ARS-CoV-2 assay Xpert Xpress SARS-CoV-2 test, COVID-19 RT-PCR test, TaqPath COVID-19 Combo kit, STANDARD M n CoV RT detection kit etc.
Basically, the COVID-19 diagnostic methods fall into two major categories: Molecular tests (direct methods) are used to detect viral genetic material (RNA) of SARS-CoV-2 using nucleic acid hybridization methods or by polymerase chain reaction (PCR) techniques. Immunological and serological assays (indirect methods) are the second category, which are used to evaluate antibody titers or detect viral antigenic proteins in individuals. Direct methods, detecting SARS-CoV-2 viral RNAs, are used to identify virus-infected people who are either asymptomatic or at the severe phase of COVID-19 infection. These methods are applied not only for contact tracing studiesbut also help to detect time-to-time emergenceof SARS-CoV-2 variants [ 54 ]. When methodically applied, contact tracing aidsintracing the chain of contagious disease transmission and is considered as anessential tool to control disease outbreaks. In contrast, indirect methods check the immunity status of individuals and communities over a period of time [ 52 , 56 , 57 ]. As a part of this review article, we reported current SARS-CoV-2 detection trends based on conventional and existing methodologies, which may assist innovations in the field of disease diagnostics.
RT-PCR is one of the foremost developed gold-standard tests used to detect viral loads of SARS-CoV-2 virus in COVID-19 pandemic [ 58 ]. It works on the basis of reverse transcriptase (RT) generating complementary DNA (cDNA) from the viral RNA template, followed by 40 cycles of exponential amplification of cDNA to double-stranded (ds) DNA. Clinical samples’ RNA levels are amplified using primer-probes designed for the targeted regions of SARS-CoV-2, including ORF1ab , OR1a , envelope (E) genes, RNA-dependent RNA polymerase (RdRP), spike (S) protein, and the nucleocapsid (N) [ 29 , 58 ]. It is a quantitative (qPCR)-based amplification method that monitors viral load in clinical samples using fluorescent or electrical signals [ 59 ]. As a result, the viral load in the form of cyclic threshold (Ct) values are determined by quantifying SARS-CoV-2 viral RNA in clinical samples(swabs) collected (under bio-safety protection 3 level) generally from individuals’ upper respiratory tract. Clinical samples with a higher viral load indicate a low Ctvalue. The cut-off Ct value is 35, below which COVID-19 positivity is considered, and the above which COVID-19 is considered negative, while Ct values ≤ 25 indicate a higher viral load [ 60 ]. These values are used to evaluate whether a person is positive for COVID-19 and to establish the status of COVID-19 patients’ isolation periods [ 34 ]. Aflow chart of RT-PCR is depicted in Figure 1 . RT-PCR kits are currently manufactured by a number of companies, allowing researchers to deal with a variety of clinical samples such as respiratory swabs, serum, saliva, stool, and ocular secretions ( Table 1 ).For COVID-19 diagnosis, customized cartridge-based amplification of nucleic acid tests (CB-NATs) and chip-based NATs have also been used. Other advancements inmolecular diagnosis of COVID-19 include nested RT-PCR and droplet digital PCR. Nested RT-PCR is an altered RT-PCR, having the merit of increased amplification specificity by reducing altered products generation due to the fact of non-specific primer binding. This technique has a testing sensitivity of 95% using low viral load samples [ 58 ]. However, this new PCR method also hassome disadvantages including being costlier than qPCR and cross-contamination-caused false-positive results [ 54 ].
Flow chart of RT-PCR--based detection of SARS-CoV-2 infection: ( 1 ) collection of the test sample from anindividual; ( 2 ) mixing the collected sample with viral transport media and storageat 4 °C until use; ( 3 ) isolation of viral RNAs from the collected sample; ( 4 ) synthesis of cDNA from viral RNA by reverse transcription; ( 5 ) RT-PCR with specific primers/fluorescent markers demonstrates either positive or negative results for SARS-CoV-2 detection.
Instead of RT-PCR, isothermal nucleic acid amplification is the method which does not require thermal cycling was developed having applications in disease diagnosis. Because of this feature, it is the quickest and most convenient molecular biology detection method for diagnosing SARS-CoV-2 infection [ 45 ]. This method enables primer-mediated polymerization of the target sequences by strand-displacement activity. Based on this principle, two additional methods were developed, which include:
This technique is a modification of isothermal nucleic acid amplification, which is specifically used to diagnose infectious diseases caused by RNA viruses [ 61 ]. It is accomplished by the three sequential steps:
RT-LAMP technique-based detection of SARS-CoV-2 infection: ( 1 ) collection ofhuman samples; ( 2 ) mixing of the collected sample with viral transport media and storageat 4 °C until use; ( 3 ) single-stranded RNA genome of SARS-CoV-2 with the targeted genes; ( 4 ) specific primers binding atthe targeted genes; ( 5 ) synthesizing the first-strand cDNA by reverse transcription; ( 6 ) DNA polymerization for second-strand cDNA synthesis; ( 7 ) dumbbell-shaped DNA formation during the process of cDNA synthesis; ( 8 ) RT-PCR with specific primers/fluorescent markers demonstrates either positive or negative results for SARS-CoV-2 detection.
Thus, this technique is one of the promising tools used for the detection of COVID-19.
It is a single tube-based isothermal nucleic acid amplification system thatworks on the principle of both RNA transcription and cDNA synthesis using RNA polymerase and reverse transcriptase simultaneously. In this method, instead of DNA amplicon, RNA amplicon is produced from the target nucleic acidin question [ 63 ]. The TMA mechanism is initiated when the template viral RNA hybridizes with specific capture probe. Upon the addition of oligonucleotides promoter site is bound by T7 RNA polymerase, this directs the oligonucleotides to capture onto magnetic microparticles under the influence of magnetic field. There by forms an active complex of T7 promoter sequence linked primer. Wherein the RNA molecule formed undergoes reverse transcription producing a cDNA. Later on, during the first strand of cDNA synthesis, the RNA strand of the hybrid RNA–cDNA is degraded byRNase H activity of the enzyme, while reverse transcriptase aids in single-stranded (ss) cDNA formation. In the final step, many RNA amplicons are produced by the action of T7 RNA polymerase [ 30 ], leading to their re-entry into the TMA process. This exponential amplification generates billions of RNA amplicons in less than 1 h ( Figure 3 ). Based on this principle, a platform called Panther fusion is used to sense ss nucleic acid detection viaa fluorophore and quencher. This platform of panther fusion is unique due to the fact of its high turnover rate (up to 1000 tests in 24 h), and this method clearly demarcates other frequent respiratory viruses causing similar symptoms of COVID-19. In addition, the availability of another version of Panther fusion, called Hologic’s Panther Fusion platform, simultaneously performs both TMA and RT-PCR for the detection of SARS-CoV-2 RNA more accurately [ 58 , 64 ].
Transcription-mediated amplification (TMA)-based detection of SARS-CoV-2 infection: ( 1 ) reverse transcription-based first-strand cDNA synthesis; ( 2 ) RNA strand of hybrid RNA–cDNA is degraded by the RNase H activity of the enzyme reverse transcriptase; ( 3 ) DNA polymerization for the synthesis of second-strand cDNA; ( 4 ) PCR amplification with specific primers will demonstrate either positive or negative results for SARS-CoV-2 virus detection (multiple arrows indicate multiple cycles of amplification).
Clustered regularly interspaced short palindromic repeats (CRISPR) are edited DNA sequences that were first noticed as chopped nucleic acids in bacteriophage-infected bacteria. Its mechanism of action was discovered while studying the bacterial defense system, which demolishes the DNA of similar bacteriophages during their subsequent infections. This specific molecular mechanism understanding led to the discovery ofCRISPR and Cas enzyme (endonuclease) technology, a cutting-edge tool facilitates precision genome editing studies in various organisms [ 65 , 66 ]. This technology gained high popularity due to the fact of its efficiency and specificity in the genome editing process, also called targeted mutagenesis [ 65 , 67 ]. Both endonuclease and synthetic guide RNA (gRNA) work together to edit (insertion/deletions) a specific DNA sequence, resulting in the altered genomes of interest [ 68 ]. Thus, endonucleases, such as Cas9, cleave the targeted DNA around theprotospacer adjacent motif (PAM), which facilitates to create interestededits in different organisms for various research applications [ 65 , 69 ]. The CRISPR/Cas tool, which is a prominent technology, is also being used to detect viral infections in humans [ 70 , 71 ]. The CRISPR system uses specific endonucleases (such as Cas12a and Cas13a) and gRNA to detect the genome of viral pathogens [ 47 , 72 ]. This CRISPR system has now been extended for the diagnosis of SARS-CoV-2 infections in humans ( Figure 4 ).
CRISPR/Cas-based detection of SARS-CoV-2 infection: ( 1 ) reverse transcription of isolated viral RNA; ( 2 ) reverse transcription for the synthesis of cDNA; ( 3 ) CRISPR-mediated genome editing (identify and cleave) actat the precise sequence of viral RNA SARS-CoV-2 genome. Both Sherlock and Detector of the CRISPR tool convert viral RNA to DNA (isothermal amplification), which activates nuclease enzyme activity (Cas-12/13) to cleave the target sequence (pink colored symbols indicate DNA polymerase;red colored symbols indicates primer); ( 4 ) loading of the sample (fluorescence RNA reporter) on to strip for detection of the specific viral RNA sequence; ( 5 ) the number of bands visible on the strip (lateral flow) represents whether the test is positive or negative for SARS-CoV-2 infection.
Specific high-sensitivity enzymatic reporter unlocking (Sherlock) and DNA endonuclease-targeted CRISPR trans reporter (Detector) are two important techniques of CRISPR for SARS-CoV-2 detection.In these techniques, instead of Cas9, either the Cas12 or Cas13 endonuclease proteins are used to cleave and identify the SARS-CoV-2 viral genetic materials [ 29 , 45 ]. Sherlock is a CRISPR/Cas13-based tool used to precisely detect viral RNA genome in COVID-19 patient samples [ 73 ], wherein Cas13 cuts the SARS-CoV-2 ORF1ab gene-targeted RNA sequence. In this process, RNA of throat/respiratory swabs/samples aresubjected to reverse transcription to synthesize cDNA based on reverse polymerase chain reaction and amplified to give products [ 48 , 54 , 74 ]. The amplified product is further transcribed into RNA amplicons. Then, specific synthetic gRNA and Cas13 complex recognize to bind the amplified RNA product [ 75 ]. The Cas13 RNA targeting enzyme activity cleaves both target and non-target nucleic acids of the patient sample. The targeted product upon binding by the fluorophore, quencher probes cleaved by activated Cas13, givea fluorescence signal [ 48 , 74 ]. The Sherlock technique reads out clinical samples to determine anoutcome within 1 h [ 76 ]. Gootenberg et al. (2017) [ 77 ] initially developed this Sherlock method; later, it was refined by Kellner et al. [ 73 ] to specifically detect the COVID-19 RNA genome. Due to the CRISPR multiplexing, the Sherlock method detects more than 160 differentpathogenic agentspresenting in patient samples [ 78 ]. While, CRISPR/Cas12 editing technology is used to detect the SARS-CoV-2 genome through the DNA endonuclease-targeted CRISPR trans reporter (detector) technique [ 79 ]. The fluorescent probe and CRISPR/Cas12 were employed to detect the differential RNA amplicons that can be used to confirm SARS-CoV-2. This technique is handy, as is can be conducted outside of the clinical diagnostic laboratory, indicating POC testing. The negative results of RT-PCR can be found to be positive in CRISPR-based fluorescent detection due to the fact of its accuracy [ 48 ].
RT-qPCR is the gold-standard test for the clinical diagnosis of SARS-CoV-2. But for the analysis of a large number of samples, there is a need for an approach that uses more stringent nucleic acid hybridization conditions which prevents their mismatch base pairing. Such developed methods overcome the RT-qPCR associated false-negative results during disease diagnosis [ 80 ]. Microarray nucleic acid hybridization is one of the basic fundamental molecular tests that encompass the use of single-stranded (ss) nucleic acids DNA/RNA as microscopic spots (chip), which hybridizes with cDNA prepared from the RNA genome of SARS-CoV-2. The labeled cDNA fluorescent probe identifies complementarySARS-CoV-2 RNA molecules present in the clinical samples. After washing, labeled probes that are hybridized with the specific nucleic acid of SARS-CoV-2 areexcited to produce a signal. Currently, this diagnostic approach is deployed for detecting mutations in single-nucleotide polymorphisms (SNPs) and genotyping of emerging SARS-CoV-2 variants [ 49 , 50 ]. As a result of its multiplexing and high specificity, DNA microarray hasbeen emerged as one of the most promising diagnostic methods for SARS-CoV-2 detection [ 81 ].
Genomic sequencing tools are aversatile platform withimplications in different scientific fields such asagriculture, public health interventions, pathogen origin, contagious disease outbreaks, and phylogenetic analysis [ 82 ]. In the process of being prepared for future public health threats, current whole genomic sequencing trends need to be explored in every COVID-19 affected nation at an accelerated rate to build a healthy global community. High throughput genomic analysisvianext-generation sequencing (NGS) ensures the identification of novel pathogens of evolutionary/zoonotic origins and their rate of mutation or recombination frequency over time [ 83 ]. Investigations on genomics and molecular epidemiology of a disease organism (2019 novel coronavirus) unravel the origin and receptor binding of host–pathogen during itsinfection process. Such investigations are the real-time basis for designing novel molecular-based diagnostics and therapies required to control pandemics [ 84 ]. Rapid SARS-CoV-2 RNA isolations, differential RNA-Seq, library preparation protocols, identification of genomic sites of antiviral resistance, and deposition of repository genomic/protein/nucleotide sequence databases are used for scaling time-to-time viral outbreak intensities [ 82 , 85 ]. The due emergence of a given virus with a different genomic sequence, when it is tested with the existing probe results in a false–negative outcome leads to non-diagnosis of COVID-19 infections. In view of the emerging SARS-CoV-2 variants, the diagnostic test failures need to be correlated by whole genomic sequencingto reveal insights into whether failures weredue to the fact of sequence divergence or test failures [ 86 ]. Therefore, advances in diagnostics and improved genomic surveillance are two goals that need to work hand in hand for examining/handlingSARS-CoV-2 transmissibility or future pandemic threats. In addition, genomic sequencing of emerging variants may not only havean impact on innovations in clinical diagnostics but could also influence real-time vaccine redesign required to immediately curtail COVID-19 infections [ 87 ]. Therefore, large-scale deployment of time-to-time viral genomic sequencing ( Figure 5 ) is required to characterize SARS-CoV-2 variations for likely diagnosis and clinical significance.
Genome sequencing for detection of SARS-CoV-2 variants: ( 1 ) swab/test sample collection from an individual; ( 2 ) mixingthe collected sample with viral transport media and storage at 4 °C; ( 3 ) isolation of viral RNA from the collected sample; ( 4 ) cDNA synthesis from viral RNA by reverse transcription; ( 5 ) PCR-aided amplification; ( 6 ) computer-aided library preparation and collection of nucleotide databases; ( 7 ) further data analysis: RNA/whole-genome sequencing via NGS to identify SARS-CoV-2 variants assist in redesigning novel molecular-based diagnostics therapies to combat COVID-19.
These are the medical gadgets that are readily used to diagnose diseases ranging from acute to chronic in nature when laboratory equipment is in short supply/lacking. Thus, biosensors serve the purpose of detecting disease diagnosis within no or limited availability of resources, representing point-of-care diagnosis. Biosensors are generally classified into different types based on the type of transducer employed or the type of bioreceptor utilized. The basic type of biosensors arecomposed of gold nanoparticles (AuNP) of 20–80 nm and are precipitated with either coronavirus surface antigens or antibodies. It works on the principle of surface plasmon resonance (SPR), wherein changes such as adsorption/detection of biologically active compounds (such as antibodies/antigens/enzymes) are converted into incident light at surface interference and transducesreadoutcome via optical, electrical, and enzymatic methods [ 29 ]. Biosensors developed to diagnose severe acute respiratory syndrome (SARS) arecomposed of biochips incorporated with surface antigens that detect 200 ng/mL antibodies in a few minutes [ 88 ]. The CANARY biosensors, which were now specifically designed to detect the COVID-19 virus by PathSensors Inc., are based on a cell-based immune biosensor that transduce to give results in 3–5 min by capturing the virusviasignal amplification. Most recently, field-effect transistor (FET)-based biosensors were established for detecting the SARS-CoV-2 viral components.It is constituted of FET-based graphene sheets coated with a specific antibodiesagainst the spike protein ofSARS-CoV-2. These FET-based biosensors have a limit of detection of 2.42 × 10 2 copies/mL in clinical samples and an LOD of 1.6 × 10 1 pfu/mL in culture medium [ 89 ]. Apart from these, the aptamer-based biosensors were developed specifically to detect SARS-CoV-2 in asymptomatic patients. Such biosensors have the features of higher sensitivity, specificity, selectivity, and cost-effectiveness [ 52 , 54 ].
These assays are commonly used to track infectious disease outbreaks by correlating past and/or present immunity status from the individual to community levels over a period of time [ 90 ]. Government officials of a given nation conduct these tests as part of a survey to assess population/herd immunity against a given infectious disease. The data generated by such survey generally aid in the epidemiological, diagnostic, and vaccine redesigning investigations [ 31 ]. These tests examine immune status by looking for two specific antibody classes (immunoglobulin G (IgG) and immunoglobulin M (Ig M)) against the most prevalent pathogenic antigens (e.g., spike protein of SARS-CoV-2) present in clinical samples such as saliva, sputum, and blood. As a front-line defense mechanism, the human immune system soon after infection produces IgM than IgG. However, IgG, on the other hand, has a long-term immunological memory and will respond to the same pathogen if it is encountered again. IgM antibodies are an early indicator of infection, whereas IgG antibodies are a current or post-infection immunity indicator [ 30 ]. In addition, immunoglobulin A (Ig A) responses in mucosal secretions are also found at greater titers. These immunoglobulin responses have prime significance in the current SARS-CoV-2 outbreak ranging from human-to-human transmission to infection monitoring at the community level [ 91 ]. In COVID-19 diagnosis, these antibodies’ presence (positive test) or absence (negative test) against SARS-CoV-2 antigens is widely diagnosed using—enzyme-linked immunosorbent assay (ELISA), lateral flow immunoassay (LFIA), and ELISpot.
LFIA is also called a lateral flow test (LFT). This is a portable device and considered a POC immunodiagnostic test ( Table 1 ). The test procedure is conducted to reveal the outcome at or near the site of the patient. It works on the principle of rapid immunochromatography, wherein a test strip is conjugated with IgM or IgG or both [ 92 ]. A positive test indicates that the person is infected with SARS-CoV-2, and a negative test indicates that he has recovered from COVID-19 [ 93 ].By dripping a few drops of whole blood clinical sample (blood + few diluting liquids called buffer), if it contains viral antigens, it will bind against the SARS-CoV-2 antibodies present in the control and assay lines of the test strip. Based on the type of antibodies present in the blood sample of the testing individual 2–3 lines of color band formation is noticed. When compared to the RT-qPCR detection, this test’s diagnostic specificity and robustness were found to be higher [ 94 ].
Among the various ELISA procedures, indirect ELISA is commonly used test platform, which comprises 96 testable antigen-impregnated microtiter wells (e.g., the spike protein of SARS-CoV-2). These antigens are customized to bind with specific antibodies (IgM or IgG) present in a COVID-19 patient’s serum sample. In the process of detection, a highly specific antigen–antibody reaction complex is formed. Following washing, such a complex combine with the conjugate (antihuman IgG with horseradish peroxidase) and the substrate (3,3′,5,5′tetramethylbenzidine) to give a color change that is readily detected by theELISA’s palate reader. A positive test signal results when the anti-COVID-19 IgG becomessandwiched between the anti-human IgG probe and absorbed antigen. Due to the merit of robust infection stage detection for antigen led to widespread use of the ELISA test to evaluate the infection status in the ongoing COVID-19 pandemic [ 95 ].
It is an antigen-specific T-cell functional test that assess cellular immunity by counting the number of T-cellresponses, which has the ability to produce specific cytokine-interferon γ [ 29 , 96 ]. During the process of SARS-CoV-2 infection, T cells are found to play a critical role in cellular immunity by providing long-term protection [ 97 ]. During the acute phase of infection, these T cells fight against the virus, among which some of them are transformed into SARS-CoV-2 specific memory cells, which restores the immunological memory needed to prevent future infections. This can be attributed to why people are protected during the second or other times of COVID-19 infection or post-vaccination [ 98 ]. This assay consists of microwell plates that are pre-coated with specific antibodies in a dilution culture medium of approximately100 µL per well, after whichthe addition of peptides of viral antigens and peripheral blood mononuclear cells (PBMCs) stimulate the required T-cell-mediated cytokine production. These cytokines accumulate around the T cells and appear as spots that are finally scanned and analyzed through the special immune-spot software [ 99 ]. Thus, the ELISpot method has viability to assess the cellular immunity status of an individual during the acute phase of COVID-19 infection.
It is a test for determining the threshold levels or quantitative capabilities of a clinical sample to induce neutralizing antibodies (NABs), which is a measure of humoral response. These NABs confer protective immunity against a disease condition [ 100 ]. In addition, the results of this assay are used to correlate clinical sample NABs titers response under a particular medical condition or immunization efficacy study against COVID-19 [ 101 , 102 ]. This assay has also been used to quantify cultured cells capabilities of producing NAB’s titers in 1–2 days or clinical samples (i.e., blood, serum, or plasma) response in hours. In infected cell cultures, NABs are known to directly interfere with viral binding (SARS-CoV-2) to prevent its entry and viral replication [ 29 ].NABs generally bind to capsid proteins of the non-enveloped viruses and glycoproteins of the enveloped viruses not only preventthe entry of the virus but also hinder conformational changes. This leads to the formation of pathogen–antibody complexes, which are phagocyted by the macrophages [ 53 ]. The latest advancements in this assay have reduced the time of detection from days to hours with the increased feasibility of testing viral disease NABs and vaccine efficacy evaluation [ 100 ].
The probable flow chart of diagnostic tests used to rule out COVID-19 infections in asymptomatic and symptomatic persons has been illustrated in Figure 6 .
Diagnostic flow chart for COVID-19 disease detection.The probable flow chart used to rule out positive or negative test results forSARS-CoV-2infections in asymptomatic and symptomatic individuals with COVID-19 [ 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 ].
RADTs are commonly used in situations where molecular detection technologies are unavailable, and they are primarily used for disease testing with symptomatic individuals ( Figure 7 ). These detection methods are simple and portable, which are based on quantitative measurements of antigenic (Ag) surface proteins in terms of either their absence (negative result) or presence (positive result) [ 54 ]. Antigen (Ag) is a foreign or pathogenic molecule that readily binds to a B-cell Ag receptor (BCR) or Ag-specific antibody (Ab). RADT works on the principle of identifying the presence of SARS-CoV-2 antigen in clinical samples using specifically designed monoclonal antibodies. The SARS-CoV-2 viral structure ( Figure 8 ) comprises a spike protein (SP), an envelope protein (EP), a major glycoprotein, a membrane protein (MP), and a nucleocapsid protein (NP), whichare the viral antigens supposed to be detected in the clinical sample for COVID-19 detection [ 54 ]. The detection of SP in the sample is the most rapidand accurate for detection of COVID-19, as it can be identified from urine or serum samples during the early stages of infection or 10 days post-infection of asymptomatic cases [ 114 ].As the NP is larger in size, a sandwich immunoassay is the most commonly used test for its detection, while MP is the most abundant viral protein used for the detection of COVID-19 disease. In addition, EP is the next abundant smallest viral protein that can used to detect COVID-19 disease [ 93 , 115 ]. If the antigen in question is present in enough concentration in the collected sample, they bind to specific antibodies which are encrypted on the test vial. Thus, within 30 min of duration, the viral antigen detection generates a visually detectable signal with a sensitivity of 34 to 80% [ 54 ].
Rapid antigen test (RAT) kit-based detection of SARS-CoV-2 infection: ( 1 ) test samples are collected in the form of swabs; ( 2 ) mixing the collected swab samples with buffer; ( 3 ) loading collected sample into the well of the antigen-coated strip; ( 4 ) formation of one band representsa negative test, and two bands represent a positive test for COVID-19 infection.
Structure of the SARS-CoV-2 virus. The structure of the COVID-19 virus contains the spike glycoprotein (SP), membrane protein (MP), nucleocapsid protein (NP), an envelope protein (EP), and single-stranded +RNA as the genome.
This test assay, based on the phenomenon of chemiluminescence (CL), is a chemical reaction in which electromagnetic radiation is generated in the form of light. The chemiluminescence technique is integrated with immunochemical reactions in the chemiluminescence immunoassay (CLIA), wherein chemical probes similar to other labeled immunoassays (such as FIA andELISA) are used to generate detectable light emission [ 116 ]. This assay uses synthetic antigens of the coronavirus SP and NP to measure antibody immune responses using a chemiluminescent analyzer [ 117 ]. Variations in the titers of SARS-CoV-2 specific antibodies (IgM and/or IgG) in COVID-19 patients represent the phase (i.e., acute or chronic) of COVID-19 infection status [ 118 , 119 ]. Thus, it is a reliable method with high diagnostic sensitivity to know the immunization status and the epidemiological surveillance [ 120 , 121 ]. Moreover, with the development of peptide-based magnetic chemiluminescence enzyme immunoassay, the Diazyme Laboratories of San Diego has advanced the Diazyme DZ-Lite-based SARS-CoV-2 IgM CLIA detection kit and SARS-CoV-2 Ig G CLIA detection kits, which run on the fully automated chemiluminescence analyzer [ 122 , 123 ]. Similarly, a technique with multiplex chemiluminescent immunoassay was found to detect all antibodies like IgG, IgM, and IgA during serological profiling of both COVID-19-positive asymptomatic and symptomatic patients [ 55 ].
Edward Jenner’s era of vaccination began with the development of the smallpox vaccine in 1976 [ 124 ]. Vaccination is an effective, economical, and the most successful health intervention that saves millions of lives every year. Vaccines are biological preparations of antigenic agents that trigger acquired immune responses in order to avert infectious diseases. Vaccine development is a tedious and complex process; it takes time to develop huge amounts of viruses on a wide scale, and it needs level 3 biosafety facilities fortheir production [ 38 ]. Vaccine development process often takes 10 to 15years, with a poor success rate [ 125 ]. Breakthrough vaccine development platforms are currently being advanced in an unthinkable time frame (12–18 months) with the hope of putting an end to the SARS-CoV-2 pandemic or its future outbreaks/surges [ 126 ]. Scientific communities across the world have been consistent in designing different platform-based vaccine candidates to curtail COVID-19disease asearly as possible [ 39 ]. Immunization against COVID-19 might be a rightful hope for ending the current epidemic, as vaccine-induced immunity is considerably more likely to confer adaptive immunity against the natural infection process or recurrent SARS-CoV-2 infections [ 127 ]. Vaccination hopes to provide long-term immunity against the deadly virus by protecting human beings from becoming ill or averting mortality due to the fact of COVID-19 infection. In all countries, vulnerable populations (elderly) are the highest priority for vaccination. The life of people can return to anormal state with contacts, social events, and traveling only after the performance of vaccination to a population proportion (70%) of herd immunity [ 43 , 128 ]. This may be attributed to development of vaccine-based immunological memory in people’s bodies, which can effectively tackle the present form of the virus and possibly against the mutated virus. If any of these vaccines become less effective against a new form of virus, then one has to change the vaccine’s composition to protect the life of people from new variants of COVID viruses. To eliminate the COVID-19 disease completely from the people, it is necessaryto collect and analyze data continuously on new variants of the COVID-19 virus. Moreover, in future, second, or third generation vaccines having antigenic preparation beyond the SARS-CoV-2 S protein or multiple antigenic targets might be worthwhile in effectively tackling and completely eradicating the SARS-CoV-2 virus from the human population.
As per the currently available data, 14 different vaccines against SARS-CoV-2 have been known to clear phase IIIclinical trials and be approved for worldwide massive and accelerated immunization campaigns to mitigate COVID-19viaEUA [ 40 , 129 , 130 ]. This is more likely to combat the mounting COVID-19 cases and deaths worldwideurgently. COVID-19 vaccine candidates developed come under different types of vaccine platforms ( Figure 9 ):
Various types of vaccine platforms used to mitigate COVID-19 pandemic. Major types of vaccine platforms: viral vector vaccines of non-replicating andreplicating types; nucleic acid vaccines based on DNA and mRNA; vaccines based on recombinant proteins/subunit/VLPs virus-like particle;vaccines based on virus-based on inactivated and live attenuated viral components.
Each type of vaccine candidate has pros and cons in terms of safety, efficacy, and development [ 35 ].
The viral vector vaccination platform uses non-infectious empty viral particles that self-assemble as infectious virions and having the ability to mimic antigenic (coronavirus) sequences. Due to the lack of a viral genome, these vaccines are empty viral particles of delivery systems containing foreign antigenic proteins (SARS-CoV-2) on their surface. These vaccines use the virus as vectors which are chemically destabilized to make them non-infectious in nature. Due to the natural tendency of host cell infection by viruses, viral vector-based vaccines have the highest ability to carry gene transduction [ 131 ]. The majority ofhuman cells are easily infected with adenoviral vectors because they have adenovirus cell surface receptors that aid in adenovirus attachment and entry into the cell. Viral vector vaccines are of either non-replicating (inactivation of viral replicating genes) or replication type. Viral vector vaccines ( Figure 10 ) express the antigenic proteins using the protein machinery of the infected cells, which evokes higher intensities of immune responses of both cellular and humoral types [ 132 ]. However, possible reversion to a pathogenic type remains a safety concern [ 133 ]. Despite this, viral vector-based vaccines are known to be produced rapidly in bulk quantities and need cold-chain requirements during vaccine storage and transportation [ 41 ].
Viral vector-based vaccines for the treatment of COVID-19: ( 1 ) modification of adenovirus by removing pathogenic genes to make them non-infectious; ( 2 ) insertion of a gene of interest encoding the SARS-CoV-2 virus’s spike protein into an adenovirus system; ( 3 ) making a modified adenovirus-based vaccine and their administration into individuals; ( 4 ) adhesion of a viral vector to human cells and delivery of the antigenic determinant; ( 5 ) expression of a viral vector antigenic determinant (spike protein) and its display on the surface of human cells; ( 6 ) recognition of viral spike protein by immune cells; ( 7 ) immune cells’ production of antibodies (NABs) against viral spike protein; ( 8 ) immune responses with elicited antibodies neutralize the SARS-CoV-2 virus in vaccinated people.
The majority of the current vaccines developed to mitigate COVID-19 come under this category. This type of vaccine is devoid of the genes necessary for replication; therefore, they cannot produce infectious progeny, posing no risk of vaccination infection [ 134 ]. These non-replicating viral vector vaccines are genetically altered adenovirus (Ad) vectors that are impaired to carry replication in humans. It is achieved by disarming viral structural proteins within the vector, thus hindering virion assembly underin vivoconditions. But the assembly of vaccine vector requires the missing structural protein from another helper virus or a transgenic host cell. Commonly used non-replicating types of viral vectors are serotype 26 (Ad26) and serotype 25 (Ad25) of human adenovirus, alphavirus, MVA-modified vaccinia virus Ankara, and adeno-associated virus (AAV) [ 134 ]. Other viruses which are used as vectors are the modified vaccinia Ankara (MVA) virus, influenza virus, human parainfluenza virus, and Sendai virus [ 135 , 136 ]. One major drawback associated with these vectors is limited vaccine efficiency due to the pre-existing immunity. However, it is circumvented by using vector types that are either uncommon in human beings [ 136 ] or by using viruses that do not induce much immunity or animal-based viruses, such as adeno-associated viruses, are used. Further, pre-existing immunity is circumvented by boosting with one vector or by priming with another vector. Several non-replicating viral-based vaccines against SARS-CoV-2 are in the final stages of clinical tests Due to the replication deficiency, greater doses of these vaccines are required to elicit an immune response. In addition, these vaccines need to be administered in booster doses to confer long-term immunity [ 40 ]. Table 2 lists vaccines of this category that were approved for large-scale immunization via EUA, to mitigate the COVID-19 pandemic.
COVID-19 Vaccines Details Enlisted with Developers/Manufacturers, Number of Doses, Efficacy, Storage, Conditional Approval, and Current Stage of Clinical Trials [ 39 , 126 , 127 ].
Sl.Number | Vaccine Brand | Type | Developers/ Manufactures and Authorization Date for EUA | Number of Doses | Gap Between the Doses | Efficacy andApproval for Age Group | Country | Storage at and Number of Doses per Vial | Storage for | Status |
---|---|---|---|---|---|---|---|---|---|---|
Viral Vector Vaccines (Replicating and Non-Replicating Virus Based Vaccines | ||||||||||
1 | Johnson & Johnson (Janssen) (JNJ- 78436735) | Viral Vector (Non replicating Human Adenovirus vector) | Johnson & Johnson 5 March 2021 | 1 | Not Applicable | 70–85% Approved for ages 18 and above | Multinational (Netherlands, US, Belgium) | 2 to 8 °C 5 Doses per Vial | 3 Months | In phaseIII trials |
2 | Oxford-Astrazeneca (AZD-1222; Covishield) | Viral Vector (Non-Replicating Viral Vector ChAdox1-S) | Oxford University-Astrazeneca 26 February 2021 | 2 | 84 Days | 70–90% Approved for ages 18 and above | Multinational (UK, Sweden, India) | 2 to 8 °C | 6 Months | Approved for restricted emergency use in India and UK |
3 | Covishield | Viral Vector (ChAdox1_nCoV-19) | Serum Institute of India Pte. Ltd. 15 February 2021 | 2 | 84 Days | 70–90% Approved for ages 18 and above | India | 2 to 8 °C | 6 Months | Approved for restricted emergency use in India |
4 | Gamaleya-Sputnik V (rAd26, rAd5) | Viral Vector (Recombinant adenovirus vaccine-rAd26, rAd5) | Gamaleya Research Institute 19 March2021 | 2 | 28 Days | 85–90% Approved for ages 18 and above | Russia | −18.5 °C (Liquid form) 2 to 8 °C (Dry form) | 3 Months | Early use in Russia, emergency use in Belarus and Argentina |
5 | Ad26.COV2.S | Viral Vector (Recombinant Replication incompetent adenovirus type 26 (Ad26) vectored vaccine encoding the SARS-CoV-2 Spike (S) Protein) | Janssen-Cilag International NV 12 March 2021 | 2 | 28 Days | 85–90% Approved for ages 18 and above | Belgium | 2 to 8 °C | 3 Months | Emergency use in Belgium |
6 | Convidecia | Non-Replicating Viral vector | Cansino Biologicals | 1 | - | 65.3% Approved for ages 18 and above | China | 2 to 8 °C | 3 Months | Limited use in China |
Nucleic Acid Based Vaccines (RNA/DNA) | ||||||||||
7 | Pfizer-BioNtech (Comirnaty BNT162b1 & BNT162b2) | mRNA in Lipid nanoparticle | Pfizer BioNtech, Fosum Pharma 31 December2020—WHO Approved | 2 | 21 Days | 90–94% Approved for ages 12 and above | Multinational (US, Canada, Mexico & Germany) | −80 to −60 °C 6 Doses per Vial | 6 Months | Approved for full use/emergency use in several countries |
8 | Moderna (mRNA-1273) | mRNA in Lipid Nanoparticle | Moderna, BARDA, NIAID 23 December 2020 | 2 | 28 Days | 90–94% Approved for ages 18 and above | US | −25 to −15 °C 10 Doses per Vial | 7 Months | Approved in Canada and Emergency use in US |
9 | Cure Vac (CVnCoV) | mRNA | Curevac | 2 | 28Days | 90% Under review by EMA | Germany | 2 to 5 °C | 3 Months | Limited use in Germany |
10 | INO-4800 | DNA Vaccine | Inovio Pharmaceuticals + International Vaccine Institute + Advaccine (Suzhou) Biopharmaceutical Co., Ltd. | 2 | 28 Days | Advanced stage of Development | China | Room Temperature | More than One year | In phaseIII trials |
Protein Based Vaccines | ||||||||||
11 | Novavax (NVX-CoV2373) | Recombinant Nanoparticle (Spike glycoprotein+ Matrix-M Adjuvanted) | Takeda Pharmaceutical Company, Japan Serum Institute of India | 2 | 28 Days | 85–90% Approved for ages 18 and above | Multinational (US, India) | 2 to 8 °C | 3 Months | In phaseIII trials |
Whole Virus Vaccines (Live Attenuated and Inactivated Virus Vaccines) | ||||||||||
12 | Sinovac (CoronaVac) | Whole-Inactivated Virus (Formalin Inactivated + Alum adjuvanted) | Sinovac Biotech-China 22 February 2021 | 2 | 3–4 Weeks | 60–75% Approved for ages 18 and above | China | 2 to 8 °C | 12 Months | Limited use in China |
13 | Bharath Biotech Covaxin (BBV152) | Whole-Inactivated Virus | Bharat Biotech—ICMR 19 April 2021 | 2 | 28 Days | 70–80% Approved for ages 18 and above | India | 2 to 8 °C | 3 Months | Approved for restricted use in emergency situation in India |
14 | Vaccine- Covilo/BBiBP-CorV/BiBP | Inactivated Virus | BBIBP by Sinopharm- Beijing Institute of Biological Products & BIBP by Sinopharm- Wuhan Institute of Biological Products 7 May2021 | 2 | 28 Days | 79.3% Approved for ages 18 and above | China | 2 to 8 °C | 3 Months | Approved in UAE, China, and Bahrain |
Unlike non-replicating viral vectors, replicating viral vectors can multiply independently in host cells; hence, a lower dose of this vaccine formulationis adequate to establish protective immunity. These vectors are developed based on attenuated strains of viruses which are modified to express a transgene (e.g., the spike protein of SARS-CoV-2) [ 51 ]. Moreover, animal viruses that do not replicate efficiently obviously cause disease manifestation in human beings that are also used to make replicating viral vectors. However, these approach-based vectors undergo multiplication in the vaccinated individuals, which induces a strong immunity in them. There are safety concerns associated with these vaccines due to the pathogenicity of the replicating viral vector vaccines, observed particularly inimmunocompromised individuals. These vectors are often administered intramuscularly or through mucosal routes (oral andintranasal), which may impart immune responses at the specific site of administration. The common replicative types of viral vectors are measles virus (MV), vesicular stomatitis virus (VSV), and adenovirus (Ad-V) [ 137 ]. Pertussis, Hepatitis B, and HPV are examples of other vaccines developed comes under this category [ 138 ].
The nucleic acid (RNA/DNA)-based vaccine represents a novel and quick low-cost-based strategy used to impart protective immunity against SARS-CoV-2 infections. In the history of vaccine development, this is the first time of using this strategy to obtain an approved vaccine (COVID-19 vaccines) in public health programs [ 139 , 140 ]. In this approach, DNA or RNA molecules are engineered to encode antigenic proteins for triggering specific immune responses [ 141 ]. Recombinant technology uses nucleic acid molecules (DNA or mRNA encoding disease-specific antigens) in properly stabilized formulations. These nucleic acid molecules (e.g., RNA) are encapsulated to provide durability during storage and transportation. Thus, DNA and mRNA vaccines are driven into the cells using different techniques such as direct injection or encapsulation in nanoparticle form. In the case of DNA vaccines, nucleic acids are circularized forms of plasmids, which alone stable enough to use in formulations. In contrast, an mRNA vaccine needs to be kept intact for their appropriate mode of action. Thus, nucleic acid molecule-based vaccines generally need grouping with appropriate delivery vehicles such as nano or microparticles. DNA or RNA molecules, once they enter the cell, initiate the synthesis of antigens and display it on the cells surface, which after recognition by the immune cells stimulate specific immune response (antibodies) of both humoral and cellular immunity [ 142 ]. Intriguingly, nucleic acid-based vaccines can beproduced on a large scale, enablingtheir quick deployment to prevent pandemics. Because of this, several biotech industries such as Pfizer, BiNTech, and Moderna were actively engaged in the nucleic acid-based development of vaccine candidates against COVID-19 [ 143 ].
DNA vaccines are produced based on plasmid DNA; it is ahighly attractive vehicle that readily undergoes transcription and translation to produce one or multiple antigens inside cells [ 144 ]. An engineered plasmid DNA vector comprises mammalian expression promoters, RNA processing elements, and gene-specific spike proteins (in the case of vaccines against COVID-19) to express the antigenic determinants in the vaccinated individual [ 145 ]. Plasmid DNA is highly stable and can be multiplied in larger quantities using host systems (e.g., Escherichia coli and Bacillus subtilis ), which makes this platform attractive for large-scale production. Moreover, as plasmid DNA is very stable at room temperature, itmakesit easy for their long-term storage and transportation conditions. To make DNA vaccines efficient, they are administered via delivery equipment, such as electroporators, and often these vectors know to impart low immunogenicity [ 146 ]. However, the predominant challenge is that these vectors induce the risk of mutations and may readily integrate into the genome of the host cell [ 132 , 135 ]. Takis Biotech, LineaRx, Applied DNA Sciences Subsidiary, and Inovio Pharmaceuticals are among the biotech companies that have adopted DNA-based vaccine platforms for the development of vaccines against SARS-CoV-2 [ 147 ]. According to a recent study, DNA vaccine candidates werefound to be effective platforms for combating the coronavirus pandemic; however, they may still need to clear regulatory hurdles before theiravailability to the public [ 148 ].
RNA vectors are relatively recent in terms of development. These vaccines contain mRNA molecules of the single-stranded form, which express genetic information of specific antigen determinant without requiring transcription [ 149 ]. When delivered into the cells of the vaccinated individual, the antigenic sequence in mRNA merely needs translation step to make its antigenic determinant (protein). The transcript of mRNA generally encompasses the gene of the interest guarded by 3′and 5′untranslated regions -polyA tail and 7-methylguanosine cap, respectively [ 150 ]. The capacity to manufacture vast amounts of mRNA transcripts using conventional methods is merit for the production of mRNA-based vaccines [ 151 ]. The objective of particular antigenic expression is served by either mRNA transcripts with modifications (synthetic) encoding the antigenic determinant of interest or self-replicating RNA ( Figure 11 ). The mRNA molecule is naturally unstable due to the fact of its single-stranded (ss) form, and it is readily degraded by the ubiquitous action of ribonucleases. For enhancing the stability of the mRNA vaccine, the mRNA molecules are initially precipitated with 80nmsized liquid nanoparticles (LNPs) andthen packed to injectable forms [ 141 , 152 ]. Phospholipids, PEG, cholesterol, and ionizable cationic lipids make up lipid nanoparticles (LNPs), which assemble to create a stable lipid bilayer that encases the mRNA molecule [ 153 ]. The mRNA vaccine candidate is much safer, as it is neither an inactivated virus nor does it possess any protein subunits of the alive SARS-CoV-2 virus.
Mechanism of mRNA-based vaccine for developing immunity against COVID-19 infection: ( 1 ) intramuscular injection of mRNA-based vaccine; ( 2 ) entry and delivery of spike protein-encoding mRNA into human cells; ( 3 ) decoding of viral mRNA into spike protein and its display on the surface of human cells; ( 4 ) recognition of viral spike protein as antigenic determinant by immune cells; ( 5 ) immune cells’ production of antibodies (NABs) against viral spike proteins; ( 6 ) immune responses elicit antibodies to neutralize the SARS-CoV-2 virus in vaccinated people.
RNA vaccines, in contrast to traditional vaccines, are a new, potent, and cost-effective platform for against viruses [ 154 ]. The mRNA-based vaccine is considered safe, as it cannot integrate into the human/host chromosome [ 155 ]. This vaccine platform has not only been rapidly produced, but it has also showed tremendous promise in recent years due to the fact of its nature of simulating a natural kind of infection process through precise antigenic expression in host systems [ 152 , 156 ]. The use of nanotechnology to encapsulate the mRNA with a lipid nanoparticle coating enables its intramuscular delivery much easier [ 144 , 151 ]. Despite this, the RNA vaccine platform is suffering with constraints oflong-term storage and transportation instability as they need stringent cold-chain conditions.
Several RNA vaccines are in development against COVID-19 disease [ 129 ]. Among them, a vaccine (mRNA-1273) has been designed based on synthetic viral mRNA, which encodes the entire spike protein of SARS-CoV-2 virus. This is known to have the ability to induce natural infection caused by the naturalSARS-CoV-2 virus. In addition, mRNA vaccines, BNT162b1 and BNT162b2, encode for the entire spike protein and RBD subunit of SARS-CoV-2, respectively. Based on phase III clinical trials data of BNT162b2 after 28 days of its first administration, RNA vaccines showed 95% efficacy against COVID-19. Due to the fact of this, the FDA has granted BioNTech and Pfizer EUA for the BNT162b2 vaccine against COVID-19 [ 157 ]. Among the various nucleic acid-based vaccines, Moderna’s mRNA-1273 (SARS-CoV-2 mRNA) vaccine has been successfully tested and utilized for immunization against COVID-19. These features suggest that mRNA-based COVID-19 vaccines are efficient, safe, and good enough in providing immunization in humans. Among the various mRNA-based vaccines, two vaccines of BioNTech/Pfizer and Moderna (mRNA-1273) were provisionally approved for usage in several countries [ 126 ]. However, these vaccines are unlikely to induce strong mucosal immunity (oral or nasal) against infectious respiratory pathogens such as SARS-CoV-2, as these vaccines are administered intramuscularly.RNA vaccines were allowedforuse via EUA for large-scale immunization in the process of mitigating the COVID-19 pandemic ( Table 2 ).
These are viral protein-based vaccines manufactured by recombinant technologies whichconsist of viral antigenic fragments (immunogens) [ 158 ]. They have no genetic materials and are thus comparatively safer compared to whole virus-based vaccines. These are divided into virus-like particle (VLP)-based vaccines, recombinant RBD-based vaccines, and recombinant spike-protein-based vaccines.
Despite several COVID-19 vaccines having beendeveloped, there is a sufficient global demand for vaccines to control the quick spread of SARS-CoV-2. Some recombinant protein-subunit vaccines against COVID-19 are in the pipeline [ 87 , 159 ]. Protein subunit vaccines are easier to produce, having been made with one or a few harmless proteins or its segments of the pathogen, whose delivery in the host system induces strong host immunity ( Figure 12 ). Insect cells, mammalian cells, yeast, and plants are the model systems used to express recombinant proteins. The extent of given antigenic protein post-translational modifications yields varies depending on the expression system. Most protein subunit-based vaccines require adjuvants to induce enhanced immune responses [ 142 ]. Hence, to boost the immune response, this type of vaccine needs adjutants, and also multiple dose administration are mandatory to enhance vaccine efficacy. It is a well-developed platform; existing approved subunit vaccines, viz., HBV and DPT [ 128 ]. Most of these vaccines employ either the full length of S protein (vaccines based on recombinant spike protein) or its receptor-binding domain (RBD) as an antigenic determinant (recombinant RBD-based vaccines). The S protein is a surface protein of the SARS-CoV-2 virus that helps in binding the virus to the host cells with the ACE2 receptor for their fusion and entry [ 10 ]. Currently, in order to induce enhanced immune responses, different vaccines are produced using the S protein as a vaccine antigenic determinant [ 160 ]. Similar to the entire S protein, the RBD fragment induces the neutralizing antibodies (NABs) but lacks other important (neutralizing) epitopes as that of the entire S protein. Thus, vaccines of RBD subunits are not as worthwhile as those of S protein vaccines [ 38 ]. At present, different types of recombinant protein-based vaccines are at the stages of preclinical trials. Some RBD-based and spike-protein-based vaccines have entered the clinical trials ( Table 2 ) [ 129 ].Clover Biopharmaceuticals Inc., developed a trimerized S protein-based subunit vaccine against COVID-19 [ 161 ].
Mechanism of spike protein-based vaccines for developing immunity against COVID-19 infection: ( 1 ) spike proteins of the SARS-CoV-2 virus is enclosed inside a capsule; ( 2 ) spike proteins are mixed with adjuvants; ( 3 ) antigen-presenting structures are made with spike proteins; ( 4 ) virus-like particles are made with native spike proteins of the SARS-CoV-2 virus. The spike protein-based vaccines arecreated using one of the above four represented protein formulations. Upon vaccination with thespike protein-based vaccine, the antigen-presenting cells recognize the virus’s spike protein and present it to immune cells (i.e., Tcells and Bcells), resulting in both cell and antibody-mediated immunity.
Virus-like particles (VLPs) vaccines are a type of recombinant vaccine made from the antigenic portion of the pathogen, which triggers required specific immune responses. VLPs are generally made with a radius of 20–200 nm, making them ideal for uptake by antigen-presenting cells (APCs) of the host system, thereby eliciting prompt T-cell responses. The interesting feature of these nano-particle-based VLP vaccines is that theyare given as intranasal vaccines spray or inhalers [ 162 ]. There are increasing investigations on vaccine development based on nanoparticles [ 163 ]. Such vaccines are proposed to have higher specificity, efficiency, and pharmacokinetic properties. But the assembly of the particles is sometimes challenging. Vaccines of this category are under usage against Human papillomavirus and Hepatitis B pathogens [ 130 ]. Novavax Inc., developed an S protein-based nanoparticle vaccine (NVX-CoV2373) that was found to be safe and effective incontrolling COVID-19 ( Table 2 ) [ 164 ].
Live inactivated and attenuated vaccines are the whole virus vaccines with several antigenic components, which induce potentially broad immune responses in the host against the virus. This is the conventional-based vaccine type that forms the basis of many existing vaccines ( Figure 13 ).
Mechanism of whole virus-based vaccine for inducing immunity against COVID-19: ( 1 ) whole or native virus-based vaccines are prepared by inactivating the whole virus; ( 2 ) whole or native virus-based vaccines are also prepared by attenuating the virus. Whole virus-based vaccines aremade with one of the above two represented protein formulations. Upon vaccination of the whole virus-based vaccine, the antigen-presenting cells recognize the inactivated or attenuated SARS-CoV-2 virus and present it to immune cells (i.e., T cells and B cells) to mediate both cell and antibody-mediated immunity.
Live attenuated vaccines are developed by using a virus in a weakened form by eitherin vivoorin vitrotechnique or by reverse type of genetic mutagenesis. As a result, the virus replicates to a limited extent, but the virus still has the ability to replicate and mimic immunogenicity similar to natural infection. After their delivery into the host system, these types of vaccines exhibit high immunological efficiency and exert wide cross-protection by inducing humoral, cell-mediated, systemic, and mucosal immunity [ 165 ]. The currently available live-attenuated virus-type vaccines include yellow fever vaccine, oral poliovirus vaccine, vaccines against mumps, measles, and rubella [ 128 ]. These vaccines need to undergo safety concerns and has tedious process while weakening the viral antigenic components [ 166 ]. Currently, a live attenuated type of vaccine for COVID-19 was developed by Codagenix/Serum Institute of India Ltd. (Farmingdale, NY, USA) via codon deoptimization, which is about to roll out for public use.
These vaccines consist of live and whole pathogen components in an inactivated or weakened form, which generates an immune response without causing any disease manifestations. These are also called killed vaccines, whose manufacturing iseasy; however, takes a long time for virus culture under biosafety level3 production facilities. These vaccines are actually weakened by subjecting to UV radiation, heat, or chemicals. β -Propiolactone is being used as an inactivating agent and additionally need adjutants, such as aluminum hydroxide, for enhanced immunogenicity.This kind of vaccine platform has been widely used over several years as inactivation renders these vaccine formulations safe. Moreover, these vaccines are non-replicating in nature and exhibit no adverse effects even in immune-compromised hosts. The existing inactivated types of vaccines act against seasonal influenza and inactivated polio vaccine, and vaccines against rabies, Japanese encephalitis, and hepatitis-A diseases [ 128 ]. When compared to live-attenuated vaccines, these vaccines induce a lower immune response; thus, they need to be given in multiple doses to boost immunity. Despite this, inactivated types of vaccines are highly immunogenic in nature and result in the immune response of the innate type. These vaccines present the whole virus to the host’s immune system, and their immune responses are triggered to matrix, envelope, nucleoprotein, and spike proteins of the SARS-CoV-2 virus.
Some of the important examples of these kind COVID-19 vaccines are Corona Vac from Sino Vac biotech from China ( Table 2 ). Sinopharm of China has produced the BBIBP-CorV vaccine, which has exhibited satisfactory results in clinical tests and proceeded to phase IIItrials in which 79.3% efficacy was shown for against COVID-19. It also has the authorization of conditional marketing (CMA) approval. Another vaccine (BBV152) from Bharath Biotech of India is currently in phase III trials, which has received EUA for itsusage across India and other countries [ 167 ].
Table 2 summarizes different COVID-19 vaccine candidates (passed through phase III trials) after EUA, which are widely used for the public in several countries (WHO drafts landscape, 2021).
4.1. mucosal vaccines.
Massive efforts have beenmade in thedevelopment of several vaccine candidates as well as their safety testing, immunogenicity levels, host protection levels, and efficacy. Within a few days of a natural SARS-CoV-2 infection or after vaccine administrationprocess in humans, serum neutralizing antibodies are generally produced inpersons [ 152 , 168 ]. Hence, an ideal vaccine forCOVID-19 is anticipated to induce high titers of antibodies that could neutralize the SARS-CoV-2 infection process. These antibodies are known as vaccine-induced neutralizing antibodies (NABs). Further, an ideal vaccine has to reduce non-NABs production by lowering the enhanced respiratory disease (ERD) potential and by minimizing antibody-dependent enhancement (ADE) potential. These potentialities will maintain life-long immunological memory and provide protection against different CoVs [ 169 ]. In conjunction, a recent report attributed the correlation of NABsto that of human protection levels from SARS-CoV-2 after COVID-19 infection [ 170 ].After natural infection, usually the host’s immune system will induce secretary immunoglobulin A (mucosal antibody of IgA type) and IgG-mediated systemic antibody-mediated immune responses.Secretory IgA protects the upper regions of the respiratory tract, whereas the IgG know to protect the lower respiratory tract [ 171 , 172 ].
Vaccine administration procedures affect a given vaccine candidate’s antigen presentation, expression, immunogenicity, and efficacy. Generally, vaccination administration conductedby parenteral routes includes subcutaneous (SC), intradermal (ID), and intramuscular (IM), whereas mucosal routes include nasal and oral [ 173 ]. Since SARS-CoV-2infectshumansviamucosal lines of the respiratory tract [ 174 ], vaccine administrationvia the mucosal (oral and/or intranasal) route might be a critical means to prevent disease COVID-19 transmission and prevention [ 175 ], because the majority of APCs, especially dendritic cells (DCs), inhabit the mucosal sites and aid in presenting antigen to Tcells, thereby initiatingappropriate immune responses [ 176 ]. In addition, IgA immunoglobulin is inhabited at mucosal sites (upper respiratory tract) to prevent pathogenic entry into the body [ 38 ]. Most of the current vaccines developed aredelivered intra-muscularly and are known to induce immunity for preventing/attenuating disease and, thus, not staving off viremia or viral shedding from the upper respiratory tract, which perpetuates due to the deprived local IgA-mediated immune responses. Thus, vaccines administered intradermally or intramuscularly induce IgG production without secretory antibodies (IgA). This is not necessarily conferring sterilizing immunity. Sterilizing immunity is a key factor in eliminating viruses and does notcarry any of the viruses. Thus, intranasal vaccine candidates that confer mucosal and/or upper respiratory tract immunity may be rightfully thought to contain the COVID-19 pandemic as the virus neither persists nor allow them to infect othersviaviral shedding. Administration of vaccines through the mucosal/nasal route could effectively prevent infection (via induction of strong mucosal immunity) as the site of infection and mode of transmission of the SARS-CoV-2 type of virus is through the mucosal/nasal site of the respiratory tract [ 174 , 177 ]. Currently, most of the COVID-19 vaccines are administered through parenteral routes; however, a range of mucosal vaccines are in the pipeline to roll out [ 178 , 179 ], which are more likely to evoke a humoral response in oral and nasal mucosa lymphoid tissues and, thus, toughening to prevent upper airway transmission by promoting sterilizing immunity required to combat COVID-19 disease.
Edible vaccines (EVs) are vaccine formulations that humans can eat to protect themselves from viral, parasite, and bacterial infections [ 180 , 181 ]. These vaccines are modified plant fruits or vegetables (edible portions) having specific antigen determinants. EVs are edible parts of modified plants’ fruits or vegetables that are expressed with antigenic determinants (vaccine determinants) at a tissue-specific level, upon their consumption by humans trigger immune responses to protect against a certain illness. The need for such EVs in large scale is increasing due to the mounting number of COVID-19 positive cases across affected countries; hence, there is a pressing need to develop an appropriate vaccine based on edible plant parts [ 182 ]. Plant-derived edible vaccines can be a feasible and appealing platform, since they are cost-effective due to the fact of their simplicity of large-scale manufacture and the ability to immunize via the mucosal route. Maintaining the cold chain is a major concern in vaccination technology, as it requires costly and laborious logistics to keep vaccines stable throughout storage and transportation process. EVs may be the best alternative to traditional vaccines because they are easy to use (oral delivery), have no patient hesitancy (as they cover all age groups), and are biofriendly [ 180 , 181 ].
The spike protein of SARS-CoV-2 is the best know antigenic target to be cloned via plant-based vectors and expressed into the plant cells of tomato, spinach, lettuce, and cucumber [ 182 ]. Attempts for the production of edible vaccines of COVID-19 were already made in a few plant systems (carrot, tomato, cucumber, and banana) for their large-scale production [ 181 , 183 ]. In addition, various plant-based vaccines have been developed, viz., virus-like particles (VLPs), multi-epitope, and mucosal vaccines [ 184 ]. Interestingly, plant-based EVs can be either for nutraceutical purpose or used to curb human diseases [ 185 ], deploying CRISPR editing technology [ 186 ]. However, several regulatory and technological limitations need to be addressed to make EVs more efficient and applicable. To meet the existing demand for vaccines, especially in the low and middle-income countries (LMICs), these plant-based edible vaccines are viable alternatives and would be the game changer to avert COVID-19pandemics.
Immunoinformatics is the science of storing, managing, and analyzing the data related to antigenic variations at the amino acid and genomic levels by comparing the data using computational tools [ 187 ]. Numerous immunoinformatics tools, such as AlgPred, VaxiJen server, ToxinPred server, and IEDB immunogenicity, are used to evaluate the allergenicity, antigenicity, toxigenicity, immunogenicity, and interferon-gamma inducing capacity of the viral constructs, respectively [ 188 ]. Thus, the information of immunoinformatics is also necessary to predict the exact site of the highest rate of mutagenesis in the spike protein-encoding genes and thereby providing a solution in designing the polyvalent COVID-19 vaccines against the multiple emerging variants of SARS-CoV-19 viruses [ 189 ].
The ability of a digital computer to perform tasks commonly associated with intelligence is known as artificial intelligence (AI). AI tools are versatile due to the fact of their application in healthcare management, particularly in COVID-19 pandemic by detecting early COVID-19 diagnosis (with the use of technologies such as machine learning, deep learning, and deep neural network) and also being used for studying Lung Abnormalities to rule out the ARDS from common pneumonia [ 190 ]. Currently, AI is used to predict the patient’s need for oxygen therapy andasymptomatic people’s tendency to develop ARDS. This can be ruled out, which is a key clinical symptom representing the severity of COVID-19 infection [ 191 ]. Now a day’s deep learning model called COVID-19 detection neural network (CovNet) is used to distinguish between COVID-19 and community-acquired pneumonia. Moreover, AI has implications for COVID-19 coronavirus vaccine redesigning deploying VAXIGN reverse vaccinology and machine language, signifying the versatility of AI to combat COVID-19 [ 192 ].
Like other viruses, the quick emergence of different mutating forms of coronavirus is now seen worldwide, which has created havoc in many countries with regard to human health and socioeconomic well-being. An accidental mutation often gives the virus improved transmissibility, and those variants (mutants) become more fit and dominant. The emergence of SARS-CoV-2 variants has caused significant human morbidities and fatalities in the initial days of pandemic due to the lack of our preparation for the rapid spread of the pandemic viruses. This is because that the greatest ability to evade human immunity is due to the decreased neutralizing antibodies against specific variants. These changes in the virus are constantly drifting due to the fact of evolutionary pressures, although more suitable variants will emerge over time. No natural process is ongoing, new varieties may settle and no longer confer the advantage of infectivity and will eventually reach its peak form of transmission. The lessons learned from viral pandemics timelines, which spilled over in humans, showed that all viruses will be stabilized after reaching the most contagious phenotype and will finally become endemic. Albeit, early and precise diagnosis of asymptomatic persons, contact tracing, and timely quarantining of infected persons are the keys to forbiddingfurther transmission of SARS-CoV-2.
To date, there is no definitive clinically approved therapeutics available; hence, the only hope is vaccine intervention to combat outbreak SARS-CoV-2. With the advent of the Edward Jenner vaccinology era, vaccine-induced immunity is only the evidence of strategic protective immunity conferred than that elicited by the natural infection. Thus, to diminish the devastating effects of the SARS-CoV-2 on society, economy, and public health, a safe and effective vaccine is of the highest priority and paramount urgency. The current extraordinary speed with which novel gene-based vaccinations are being developed would quickly put an end to viral replication and spread. SARS-CoV-2 variants are not found to evolve at a level to minimize the acquired immunity conferred by now available COVID-19 vaccines, which roll out via EUA. However, the scientific community should rigorously keep monitoring to promptly diagnose the emergence of “vaccine-piercing”variants and, in that case, rapidly redesign diagnostics and vaccines accordingly using advanced areas of immune-informatics and artificial intelligence.
Additionally, the type (heat-stable vaccines) and route (mucosal-oral andintranasal) of vaccine administration would be viable options to avert the COVID-19 pandemic. Hence, variant-specific updating of diagnostics and vaccines should go hand in hand to come out of this public health emergency. Thus, an optimized COVID-19 immunization provides an expectation for an end to this pandemic disease, with equal access and optimal shots for people of all ages, especially in the world’s most densely populated nations (LMICs). Regardless of political ideologies and socio-sanitary settings, integrative perspectives may not be overlooked. Furthermore, to defeat the invisible enemy, SARS-CoV-2, optimizing the human lifestyle with a balanced diet, adequate sleep cycle, and physical activity are critical. As timing going, more reliable clinic treatments will also be developed for treated patients with COVID infection, which include but are not limited to new pharmaceutical drugs and CRISPR-based diagnosis and treatments using various CRISPR/Cas tools [ 193 ]. We believe that humans will eventually win this battle and that all the current chaos will be brought under control.
M.A. is grateful to the Department of Biotechnology, Telangana University, Nizamabad, for providing the facilities. P.J. is grateful to the Council of Scientific andIndustrial Research (CSIR), Government of India, for providing the Research Associate Fellowship (No. 09/0384(11496)/2021-EMR-I).
Conceptualization, M.A. and B.Z.; writing and original draft preparation, M.A., G.K.R., P.J. and S.S.; review and editing, B.Z. All authors have read and agreed to the published version of the manuscript.
This research received no external funding.
Data availability statement, conflicts of interest.
The authors declare no conflict of interest.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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2019, Current Research in Biotechnology
Biotechnology is an evolving research field that covers a broad range of topics. Here we aimed to evaluate the latest research literature, to identify prominent research themes, major contributors in terms of institutions, countries/re-gions, and journals. The Web of Science Core Collection online database was searched to retrieve biotechnology articles published since 2017. In total, 12,351 publications were identified and analyzed. Over 8500 institutions contributed to these biotechnology publications, with the top 5 most productive ones scattered over France, China, the United States of America, Spain, and Brazil. Over 140 countries/regions contributed to the biotechnology research literature, led by the United States of America, China, Germany, Brazil, and India. Journal of Bioscience and Bioengineer-ing was the most productive journal in terms of number of publications. Metabolic engineering was among the most prevalent biotechnology study themes, and Escherichia coli and Saccharomyces cerevisiae were frequently used in biotechnology investigations, including the biosynthesis of useful biomolecules, such as myo-inositol (vitamin B8), mono-terpenes, adipic acid, astaxanthin, and ethanol. Nanoparticles and nanotechnology were identified too as emerging biotechnology research themes of great significance. Biotechnology continues to evolve and will remain a major driver of societal innovation and development.
ASHOK PANDEY
Applied Biochemistry and Microbiology - APPL BIOCHEM MICROBIOL-ENGL T
Abdullahi Hassan
Current Developments in Biotechnology and Bioengineering
saumya khare
ADURI PRAKASH REDDY
Biolife 2(3):905-916
Shabir Wani , Saroj Sah
Scientists worldwide are continuing to discover unique properties of every day materials at the submicrometer scale. This size domain is better known as nanometer domain and technology concerned with this is known as nanotechnology that involves working with particles at nano level. One of the most important emerging fields of science in this centur y is Nanotechnology. It deals with designing, construction, investigation and utilization of systems at the nanoscale. The interface between nanotechnology and biotechnology is nanobiotechnology, which exploits nanotechnology and biotechnology to analyse a nd create nanobiosystems to meet a wide variety of challenges and develops a wide range of applications. Biotechnology gives us a way to understand biological system and to utilize our knowledge for industrial manufacturing. Nanotechnology has great potent ial and by the help of its application it can enhance the quality of life through in various fields like agriculture and the food system. Around the world, it has become the future of any nation. Important tools used in nanotechnology and application of nanobiotechnology in agriculture sector will be discussed in this review.
Revista Peruana de Biología
Gretty K Villena Chavez
Rahul J Desale
Anand Kumar Thakur
Jay D Keasling
theppanya charoenrat
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Scripown publication, New Delhi
Arulmozhi Ranjan
Yusuf Deeni , MICHELE MAFFIA
Hwa A. Lim, "Biotechnology - Past, present and future", Symbiosis, October 2004, pp. 31-34.
Hwa A . Lim
World Journal of Pharmaceutical Sciences
Nanobiotechnology in Food: Concepts, Applications and Perspectives
Zahra Sayyar
Journal of the National Science Foundation of Sri Lanka
Ranjan Ramasamy
Rashid Amin
Martin Philbert
melissa Tielke
book chapter
Abrar Hussain
Biotechnology Journal
Mohamad Faizal Ibrahim
Wei-Seng Ho
BioEnergy Research
International Journal of Current Microbiology and Applied Sciences
Ranjeet Verma
Stylianos Anestis
Food Technology and Biotechnology
Karl Friedl
G.Ali Mansoori
anchal srivastava
Master's thesis.
The master's degree programme concludes with a master's thesis of 35 weeks duration that includes a written report and oral presentation. The topic of the thesis can be chosen according to the student's interests in the field of biotechnology.
Important: the master's thesis needs to completed in a different group or company department - and supervised by a different professor - than the research project or industry internship!
Remuneration
In general, students are not allowed to be paid for their master's thesis. Please refer to the respective Download ETH Directive (PDF, 23 KB) vertical_align_bottom
Though, students are allowed to accept payment if they have an internship contract for up to 80%. A full-time position remains forbidden.
The master's thesis is conducted in a research group at D-BSSE. Students are expected to contact the research group they are interested in directly. Usually, the contact person for research project/master thesis is a senior assistant or post-doc in the group.
The master's thesis is a graded semester performance. A failed master's thesis can only be repeated once. If the master's thesis is repeated, a new research topic needs to be found. Students can choose the same supervisor again or a different supervisor. A passed master's thesis cannot be repeated.
Students need to fulfil the following prerequisites prior to starting their master's thesis:
The Director of Studies may allow exceptions with regard to the required 64 ECTS if cogent grounds are submitted at the proper time. Note that no exception can be made with regard to the completion of BSc programme and additional requirements.
Students need to register the master's thesis including all required information prior to the start.
The master's thesis needs to be registered in myStudies. A fter the initial registration, the request is forwarded to the supervising professor for confirmation - students are asked to inform their supervisor when they have registered the thesis.
The registration must be done in the semester in which the thesis is started. Students starting in between semesters should register the thesis in the semester in which most of the work is completed.
In a subsequent semester, the thesis does not have to be registered for again, and students may request a leave of absence .
Completing the master's thesis outside D-BSSE requires approval of the Director of Studies.
Students who wish to complete the master's thesis outside D-BSSE need to submit the respective request form together with a one-page project description to the Student Administration.
The request must be submitted in a timely manner to ensure the assessment and approval as well as the subsequent registration can be completed before the start of the thesis.
All forms can be found under Documents & Templates
NDA / Agreement
A confidentiality agreement may be requested by the external institution. Any agreement is subject to negotiations between the student, the host institution and the supervising professor. Students must clarify NDA/agreement questions in advance and be aware that ETH professors may refuse to sign any agreement other than the standard ETH templates:
The master's thesis duration is 35 weeks full-time. Thereof, 3 weeks are reserved for writing the report and 2 weeks for compensation of public holidays, sick leave and other unplanned short term absences. In case of late submission, the master's thesis is failed.
For reasons of fairness and comparability it is not allowed to change the allotted duration. Students may voluntarily extend their stay in the research group or company after submission of the master's thesis. However, the master’s thesis work and report, and consequently the assessment must only refer to the official duration.
The Director of Studies may extend the deadline if cogent grounds are submitted at the proper time.
The master's thesis is supervised by a D-BSSE professor.
The supervising professor defines the task, start date and grading criteria and evaluates the thesis. The master's thesis must show a clear innovative character with regard to the technical and scientific approach.
Mind that the master's thesis needs to completed in a different group or company department - and supervised by a different professor - than the research project or industry internship!
The master's thesis is concluded with an oral presentation and a written report.
The master's thesis needs to adhere to common scientific and academic standards.
Details are to be discussed and agreed upon with the supervising professor. There are no department specific rules, criteria with regard to the written report. It is suggested to ask the supervising professor for a good sample report beforehand and afterwards for feedback to improve own writing skills for future reports/theses.
The oral presentation may be held within a reasonable timeframe after submission of the written report. The supervising professor and the student jointly agree on a date for the oral presentation. Note that feedback from the oral presentation may not be used or integrated in the written report.
Students submit the master's thesis to the supervising professor.
The D-BSSE does not receive copies of the master's thesis.
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Table of Contents:
Current research in biotechnology: Exploring the biotech forefront . Biotechnology is an evolving research field that covers a broad range of topics. Here we aimed to evaluate the latest research literature, to identify…
Highlights – View PDFCurrent research in biotechnology: Exploring the biotech forefrontUnder a Creative Commons licenseopen accessHighlights•Biotechnology literature since 2017 was analyzed. •The United States of America, China, Germany, Brazil and India were most productive. •Metabolic engineering was among the most prevalent study themes. •Escherichia coli and Saccharomyces cerevisiae were frequently used. •Nanoparticles and nanotechnology are trending research themes in biotechnology. AbstractBiotechnology is an evolving research field that covers a broad range of topics. Here we aimed to evaluate the latest research literature, to identify prominent research themes, major contributors in terms of institutions, countries/regions, and journals. The Web of Science Core Collection online database was searched to retrieve biotechnology articles published since 2017. In total, 12,351 publications were identified and analyzed. Over 8500 institutions contributed to these biotechnology publications, with the top 5 most productive ones scattered over France, China, the United States of America, Spain, and Brazil.
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BMC Biotechnology is an open access, peer-reviewed journal that considers articles on the manipulation of biological macromolecules or organisms for use in …
All manuscripts must contain the following sections under the heading ‘Declarations’: Ethics approval and consent to participate Consent for publication Availability of data and materials Competing interests Funding Authors’ contributions Acknowledgements Authors’ information (optional)Please see below for details on the information to be included in these sections. If any of the sections are not relevant to your manuscript, please include the heading and write ‘Not applicable’ for that section. Ethics approval and consent to participateManuscripts reporting studies involving human participants, human data or human tissue must: include a statement on ethics approval and consent (even where the need for approval was waived) include the name of the ethics committee that approved the study and the committee’s reference number if appropriateStudies involving animals must include a statement on ethics approval and for experimental studies involving client-owned animals, authors must also include a statement on informed consent from the client or owner.
Looking for some unique ideas for your paper on biotechnology? Check out the list of suggestions provided in the article and feel free to take your pick.
A Selection Of Great Research Paper Topics On Biotechnology – Like a student, you’ll frequently need to write complex academic assignments that need effort, search, critically planning and exploring new aspects. You are able to only produce a winning assignment if you opt to talk about fresh ideas and new breakthroughs. Its likely the first couple of topics which come for your mind under this subject could be already taken. You have to make certain the niche you decide to address is exclusive and fresh. If other scientific study has already spoken relating to this before you decide to, then there’s no reason on paper it.
Free Term Papers On Biotechnology – Writing a good paper on biotechnology is a challenging task. If you struggling to complete it, be sure to take a quick look at the following article.
You can find free research papers online as well. There are several documents that are available online. You can download them. You can check the image search as well if you are having trouble locating one. Try typing it into the search engine of the web browser and the image browser for the best results.
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Get more information about Current Research in Biotechnology. Check the Author information pack on Elsevier.com.
INTRODUCTION Current Research in Biotechnology is definitely an worldwide peer reviewed journal dedicated to publishing original research and short communications caused by research in Analytical biotechnology, Plant biotechnology, Food biotechnology, Energy biotechnology, Ecological biotechnology, Systems biology, Nanobiotechnology, Tissue, cell and path engineering, Chemical biotechnology, and Pharmaceutical biotechnology. The Journal publishes Research Papers, Short Communications, Graphical Reviews and Reviews. We offer the “Your Paper The Right Path” Elsevier guideline which enables authors to submit their primary manuscript file with no formatting needs. Research Papers aren’t limited in dimensions. However, we all do highly recommend to authors to become as succinct as you possibly can within the welfare from the readers and also the distribution from the work. Short Communications possess the following soft limits. The manuscript should ideally contain a maximum of 4-6 Figures/Tables and 4000 words, such as the title page, all parts of the manuscript (such as the references), and Figure/Table legends.
The aim or goal and objective of the biotechnology research proposal should give a broad indication of the expected research outcome and the hypothesis to be tested can also be the aim of your study. The objective can be categorized as primary and secondary according to the parameters and tools used to achieve the goal.
Writing an investigation proposal in our era is definitely an entirely challenging mission due to the constant evolution within the research design and the necessity to incorporate innovative concepts and medical advances within the methodology section. A properly-formatted research proposal in the area of biotechnology is going to be written based on the needed guidelines forms the mainstay for that research, and therefore proposal writing is a vital step while performing research. The primary objective in preparing an investigation proposal would be to obtain approval from the 3 committees like the ethics committee and grant committee.
Research Papers – Learn more about research papers for the Master of Biotechnology Program at Northwestern University.
Alison Chow et al., “Metabolic engineering of the non-sporulating, non-solventogenic Clostridium acetobutylicum strain M5 to produce butanol without acetone demonstrate the robustness of the acid-formation pathways and the importance of the electron balance”, Metabolic Engineering 2008.
Natural Products and Biotechnology (NatProBiotech) is an International Journal and only accepting English manuscripts. NatProBiotech publishes original research articles and review articles only.
Natural Products and Biotechnology (Nat. Pro. Biotech. ) (ISSN: 2791-674X) is an International Journal and only accepting English manuscripts. Natural Products and Biotechnology publishes original research articles and review articles only and publishes twice a year. There is no fee for article submission, article processing, or publication processes. Please write the article in good English. Choose only one of the British or American usage, you should not use both together. If the language of the article is not good enough, please have it edited by anEnglish Language Editing service. The article will be reviewed by the Spelling and Language editor, if the editor decides that it is not written in good English, your article will be send to corresponding author for edit before the referee process. Research articles should report the results of original research. The article should not have been published elsewhere. Review articles should cover current topics and comply with the journal’s publication guidelines and should not have been published anywhere before.
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How to publish your research paper in an international journal
Step-By-Step Guide To Becoming a Biotechnologist
Basic Steps in the Research Process
Biotechnologists identify practical uses of biological material – including the physical, chemical, and genetic properties of cells – to improve agricultural, environmental, or pharmaceutical products, although biotechnologists also work in related capacities, as in marine biotechnology. ...
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Home > Life Sciences > Microbiology and Molecular Biology > Theses and Dissertations
Theses/dissertations from 2024 2024.
Characterization of Cellular Metabolism Regulation by the Transcription Factor Centromere Binding Factor 1 (Cbf1) , Spencer Ellsworth
Elucidating the Architecture of the TclIJN Complex that Converts Cysteine to Thiazoles in the Biosynthesis of Micrococcin , Diana G. Calvopina Chavez
Manipulating and Assaying Chromatin Architecture Around Enhancer Elements in vivo , John Lawrence Carter
Halophilic Genes that Impact Plant Growth in Saline Soils , Mckay A. Meinzer
Characterizing Stress Granule Regulation by PAS Kinase, Ataxin-2 and Ptc6 and Investigating the Lifespan of Covid-19 Virus on Currency , Colleen R. Newey
Changes in RNA Expression of HuT78 Cells Resulting From the HIV-1 Viral Protein R R77Q Mutation , Joshua S. Ramsey
Biofilm Characterization and the Potential Role of eDNA in Horizontal Gene Transfer in Hospital and Meat Isolates of Staphylococcus aureus and Their Biofilms , Ashley Lynne Ball
Novel Patterns for Nucleosome Positioning: From in vitro to in vivo , David Andrew Bates
The Effects of Polymorphisms of Viral Protein R of HIV-1 on the Induction of Apoptosis in Primary Cells and the Characterization of Twelve Novel Bacillus anthracis Bacteriophage , Jacob D. Fairholm
Analysis of the Cytopathogenic Effect of Different HIV-1 Vpr Isoforms on Primary Human CD4+ T Cells and a Model Cell Line , Jonatan Josue Fierro Nieves
The Role of Chitinase A in Mastitis-Associated Escherichia coli Pathogenesis , Weston D. Hutchison
Big Data Meta-Analyses of Transcriptional Responses of Human Samples to Orthohantavirus Infection and Shotgun Metagenomics From Crohn's Disease Patients. , John L. Krapohl
An Exploration of Factors that Impact Uptake of Human Papillomavirus Vaccines , David Samuel Redd
Genomic Analysis and Therapeutic Development of Bacteriophages to Treat Bacterial Infections and Parasitic Infestations , Daniel W. Thompson
The Use of Nucleotide Salvage Pathway Enzymes as Suitable Tumor Targets for Antibody-Based and Adoptive Cell Therapies , Edwin J. Velazquez
Comparative Sequence Analysis Elucidates the Evolutionary Patterns of Yersinia pestis in New Mexico over Thirty-Two Years , M. Elizabeth Warren
Regulation of T Cell Activation by the CD5 Co-Receptor and Altered Peptides, Characterization of Thymidine Kinase-Specific Antibodies, and Integrating Genomics Education in Society , Kiara Vaden Whitley
Evolution and Selection: From Suppression of Metabolic Deficiencies to Bacteriophage Host Range and Resistance , Daniel Kurt Arens
Identifying Sinorhizobium meliloti Genes that Determine Fitness Outcomes , Alexander B. Benedict
Pushing the Limits of SARS-CoV-2 Survival: How SARS-CoV-2 Responds to Quaternary Ammonium Compounds and Wastewater , Benjamin Hawthorne Ogilvie
Mutations in HIV-1 Vpr Affect Pathogenesis in T-Lymphocytes and Novel Strategies to Contain the Current COVID-19 Pandemic , Antonio Solis Leal
Staphylococcus aureus Metal Acquisition in Milk and Mammary Gland Tissue , Shalee Killpack Carlson
Antimicrobial Peptide Development: From Massively Parallel Peptide Sequencing to Bioinformatic Motif Identification , Alexander K. Erikson
A Comparison of Chikungunya Virus Infection, Dissemination, and Cytokine Induction in Human and Murine Macrophages and Characterization of RAG2-/-γc-/- Mice as an Animal Model to Study Neurotropic Chikungunya Disease , Israel Guerrero
The Effects of Immune Regulation and Dysregulation: Helper T Cell Receptor Affinity, Systemic Lupus Erythematosus and Cancer Risk, and Vaccine Hesitancy , Deborah K. Johnson
Identification of Genes that Determine Fitness, Virulence, and Disease Outcomes in Mastitis Associated Eschericia coli , Michael Andrew Olson
Investigation of Thymidine Kinase 1 in Cancer Progression , Eliza Esther King Bitter
Ribosomally Synthesized and Post-Translationally Modified Peptides as Potential Scaffolds for Peptide Engineering , Devan Bursey
Bioaerosols Associated with Evaporative Cooler Use in Low-Income Homes in Semi-Arid Climates , Ashlin Elaine Cowger
PAS Kinase and TOR, Controllers of Cell Growth and Proliferation , Brooke Jasmyn Cozzens
Regulation of Immune Cell Activation and Functionby the nBMPp2 Protein andthe CD5 Co-Receptor , Claudia Mercedes Freitas
Characterizing Novel Pathways for Regulation and Function of Ataxin-2 , Elise Spencer Melhado
Interactions Between the Organellar Pol1A, Pol1B, and Twinkle DNA Replication Proteins and Their Role in Plant Organelle DNA Replication , Stewart Anthony Morley
SNFing Glucose to PASs Mitochondrial Dysfunction: The Role of Two Sensory Protein Kinases in Metabolic Diseases , Kai Li Ong
Characterizing the Function of PAS kinase in Cellular Metabolism and Neurodegenerative Disease , Jenny Adele Pape
Isolation, Characterization, and Genomic Comparison of Bacteriophages of Enterobacteriales Order , Ruchira Sharma
Isolation, Genetic Characterization and Clinical Application of Bacteriophages of Pathogenic Bacterial Species , Trever Leon Thurgood
Investigation of Therapeutic Immune Cell Metabolism , Josephine Anna Tueller
Innate Immune Cell Phenotypes Are Dictated by Distinct Epigenetic Reprogramming , Kevin Douglas Adams
Bacteriophages for Treating American Foulbrood and the Neutralization of Paenibacillus larvae Spores , Thomas Scott Brady
Methods for Detection of and Therapy for Carbapenem-Resistant Enterobacteriaceae , Olivia Tateoka Brown
The Diversity Found Among Carbapenem-Resistant Bacteria , Galen Edward Card
Exploration of Antimicrobial Activity in Natural Peptides and High-Throughput Discovery of Synthetic Peptides , Emma Kay Dallon
Gut Microbiota Regulates the Interplay Between Diet and Genetics to Influence Insulin Resistance , Jeralyn Jones Franson
The Antimicrobial Properties of Honey and Their Effect on Pathogenic Bacteria , Shreena Himanshu Mody
The Ability of Novel Phage to Infect Virulent Bacillus anthracis Isolates , Hyrum Smith Shumway
Galleria Mellonella as an Alternate Infection Model for Burkholderia Species and a Comparison of Suspension and Surface Test Methods for Evaluating Sporicidal Efficacy , Joseph D. Thiriot
The Clinical Significance of HPRT as a Diagnostic and Therapeutic Biomarker for Hematological and Solid Malignancies , Michelle Hannah Townsend
Biomarker Analysis and Clinical Relevance of Thymidine Kinase 1 in Solid and Hematological Malignancies , Evita Giraldez Weagel
Hospital and meat associated Staphylococcus aureus and Their Biofilm Characteristics , Trevor Michael Wienclaw
Comparison of Cytokine Expression and Bacterial Growth During Periparturient and Mid Lactation Mastitis in a Mouse Model , Rhonda Nicole Chronis
Influence of Epstein-Barr Virus on Systemic Lupus Erythematosus Disease Development and the Role of Depression on Disease Progression , Caleb Cornaby
The Effects of Nucleosome Positioning and Chromatin Architecture on Transgene Expression , Colton E. Kempton
Phosphate Signaling Through Alternate Conformations of the PstSCAB Phosphate Transporter , Ramesh Krishna Vuppada
Acetobacter fabarum Genes Influencing Drosophila melanogaster Phenotypes , Kylie MaKay White
The Path to Understanding Salt Tolerance: Global Profiling of Genes Using Transcriptomics of the Halophyte Suaeda fruticosa , Joann Diray Arce
Genetic and Biochemical Analysis of the Micrococcin Biosynthetic Pathway , Philip Ross Bennallack
Characterizing Interaction Between PASK and PBP1/ ATXN2 to Regulate Cell Growth and Proliferation , Nidhi Rajan Choksi
The Activity of Alkaline Glutaraldehyde Against Bacterial Endospores and Select Non-Enveloped Viruses , Justen Thalmus Despain
The Role of Viral Interleukin-6 in Tumor Development of Kaposi's Sarcoma-Associated Herpesvirus Lymphomas , Rebecca A. Fullwood
The Role of the Transcriptional Antiterminator RfaH in Lipopolysaccharide Synthesis, Resistance to Antimicrobial Peptides, and Virulence of Yersinia pseudotuberculosis and Yersinia pestis , Jared Michael Hoffman
A CryAB Interactome Reveals Clientele Specificity and Dysfunction of Mutants Associated with Human Disease , Whitney Katherine Hoopes
The pmrHFIJKLM Operon in Yersinia pseudotuberculosis Enhances Resistance to CCL28 and Promotes Phagocytic Engulfment by Neutrophils , Lauren Elizabeth Johnson
Characterization of Five Brevibacillus Bacteriophages and Their Genomes , Michael Allen Sheflo
Analysis of Nucleosome Isolation and Recovery: From In Silico Invitrosomes to In Vivo Nucleosomes , Collin Brendan Skousen
Human Herpesvirus 6A Infection and Immunopathogenesis in Humanized Rag2 -/-γc-/- Mice and Relevance to HIV/AIDS and Autoimmunity , Anne Tanner
Identifying and Characterizing Yeast PAS Kinase 1 Substrates Reveals Regulation of Mitochondrial and Cell Growth Pathways , Desiree DeMille
The Detection and Molecular Evolution of Francisella tularensis Subspecies , Mark K. Gunnell
Isolation and Host Range of Staphylococcus aureus Bacteriophages and Use for Decontamination of Fomites , Kyle C. Jensen
The Antioxidant and DNA Repair Capacities of Resveratrol, Piceatannol, and Pterostilbene , Justin Ryan Livingston
High Salinity Stabilizes Bacterial Community Composition and Activity Through Time , Tylan Wayne Magnusson
Advancing Phage Genomics and Honeybee Health Through Discovery and Characterization of Paenibacillaceae Bacteriophages , Bryan Douglas Merrill
Specialized Replication Operons Control Rhizobial Plasmid Copy Number in Developing Symbiotic Cells , Clarice Lorraine Perry
Gene Networks Involved in Competitive Root Colonization and Nodulation in the Sinorhizobium meliloti-Medicago truncatula Symbiosis , Ryan D. VanYperen
Snf1 Mediated Phosphorylation and Activation of PAS Kinase , Bryan D. Badal
Studies of PhoU in Escherichia coli: Metal Binding, Dimerization,Protein/Protein Interactions, and a Signaling Complex Model , Stewart G. Gardner
Pharmacologic Immunomodulation of Macrophage Activation by Caffeine , Ryan Perry Steck
Analysis of Nucleosome Mobility, Fragility, and Recovery: From Embryonic Stem Cells to Invitrosomes , Ashley Nicolle Wright
Enhancing Protein and Enzyme Stability Through Rationally Engineered Site-Specific Immobilization Utilizing Non-Canonical Amino Acids , Jeffrey Chun Wu
Thymidine Kinase 1: Diagnostic and Prognostic Significance in Malignancy , Melissa Marie Alegre
Promoter Polymorphisms in Interferon Regulatory Factor 5 , Daniel N. Clark
Modulators of Symbiotic Outcome in Sinorhizobium meliloti , Matthew B. Crook
Evidences for Protein-Protein Interactions Between PstB and PhoU in the Phosphate Signaling Complex of Escherichia coli , Kristine Dawn Johns
Identification of the Binding Partners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactions and Non-Redundant Roles for Small Heat Shock Proteins , Kelsey Murphey Langston
A Quadruplex Real-Time PCR Assay for the Rapid Detection and Differentiation of the Burkholderia pseudomallei Complex: B. mallei , B. pseudomallei , and B. thailandensis , Chinn-woan Lowe
The Role of Nuclear BMP2 in the Cell Cycle and Tumorigenesis , Brandt Alan Nichols
Nuclear BMP2 and the Immune Response , Daniel S. Olsen
Hypersaline Lake Environments Exhibit Reduced Microbial Dormancy , Joshua Christopher Vert
Characterization of the Cellular and Organellar Dynamics that Occur with a Partial Depletion of Mitochondrial DNA when Arabidopsis Organellar DNA Polymerase IB is Mutated , John D. Cupp
Effect of Antioxidants and Oxidative Stress on Different Cancer Cell Types , Gaytri Devi Gupta Elera
Effects of Chemical Stimulation and Tumor Co-Incubation on Macrophage Activation and Aggressiveness, Measured Through Phagocytosis and Respiratory Burst , Bo Marcus Gustafsson
Loss of the Lipopolysaccharide Core Biosynthesis rfaD Gene Increases Antimicrobial Chemokine Binding and Bacterial Susceptibility to CCL28 and Polymyxin: A Model for Understanding the Interface of Antimicrobial Chemokines and Bacterial Host Defense Avoidance Mechanisms , Cynthia S. Lew
Partial Characterization of the Antimicrobial Activity of CCL28 , Bin Liu
Characterizing the Role of HspB2 in Cardiac Metabolism and Muscle Structure Using Yeast and Mammalian Systems , Jonathan Paul Neubert
Humanized Mice as a Model to Study Human Viral Pathogenesis and Novel Antiviral Drugs , Freddy Mauricio Sanchez Tumbaco
Transgene Delivery via Microelectromechanical Systems , Aubrey Marie Mueller Wilson
Antioxidants in Cancer Research and Prevention: Assay Comparison, Structure-Function Analysis, and Food Product Analysis , Andrew Robert Garrett
Characterization of the Role Nuclear Bmp2 (nBmp2) Plays in Regulating Gene Expression , Fialka Grigorova
Effects of Diabetic State and Gender on Pro-Inflammatory Cytokine Secretion by Human Macrophages Infected with Burkholderia pseudomallei , Annette J. Blam
Organellar DNA Polymerases Gamma I and II in Arabidopsis thaliana , Jeffrey M. Brammer
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Evolution of the legume flower: case studies in the early-branching papilionoid legumes (papilionoideae, leguminosae) , investigating the genetic architecture of complex traits in soay sheep , dgcr8-dependent control of antiviral immunity in human cells , evaluating assumptions & predicting impact in antimicrobial resistance research , optogenetic manipulation of cellular energetics in escherichia coli , genetic validation of the function of pfemp1 in plasmodium falciparum rosette formation , deciphering essential roles of camp signalling during malaria parasite transmission , elucidating the arabidopsis phytochrome a shade-signaling mechanism , specificity and mechanism of rna trafficking from mouse to bacteria in the gut , single-cell physiological response of escherichia coli to suppressive antibiotic combinations , hob3 is required for sapk pathway dependent gef1 plasma membrane recruitment , mechanisms of pericentromeric crossover inhibition , development of high throughput metabolomics to aid the synthetic biology 'design-build-test-learn' cycle , improving monoclonal antibody production from chinese hamster ovary cells , enhancing glycosylated triterpenoid production in saccharomyces cerevisiae , biosynthesis of metallic nanoparticles for use in anti-corrosion and anti-fouling agents , exploring s-nitrosoglutathione reductase function in the non-vascular plant, marchantia polymorpha , bioengineering inducible gene expression in leafy brassicas to address post-harvest-specific requirements , sex determination, sex chromosomes, and supergenes: evolution of an unusual reproductive system , super-resolution imaging of proteins in live cells using reversibly interacting peptide pairs .
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Research in biotechnology can helps in bringing massive changes in humankind and lead to a better life. In the last few years, there have been so many leaps, and paces of innovations as scientists worldwide worked to develop and produce novel mRNA vaccinations and brought some significant developments in biotechnology. During this period, they also faced many challenges. Disturbances in the supply chain and the pandemic significantly impacted biotech labs and researchers, forcing lab managers to become ingenious in buying lab supplies, planning experiments, and using technology for maintaining research schedules.
How research is being done is changing, as also how scientists are conducting it. Affected by both B2C eCommerce and growing independence in remote and cloud-dependent working, most of the biotechnology labs are going through some digital transformations. This implies more software, automation, and AI in the biotech lab, along with some latest digital procurement plans and integrated systems for various lab operations.
Look at some of the top trends in biotech research and recent Biotechnology Topics that are bringing massive changes in this vast world of science, resulting in some innovation in life sciences and biotechnology ideas .
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Biotechnology is a fascinating subject that blends biology and technology and provides a huge chance to develop new ideas. However, before pursuing a career in this field, a person needs to complete a number of studies and have a thorough knowledge of the matter. When we begin our career must we conduct study to discover some innovative innovations that could benefit people around the world. Biotechnology is one of a variety of sciences of life, including pharmacy. Students who are pursuing graduation, post-graduation or PhD must complete the research work and compose their thesis to earn the satisfaction in their education. When choosing a subject for biotechnology-related research it is important to choose one that is likely to inspire us. Based on our passion and personal preferences, the subject to study may differ.
In its most basic sense, biotechnology is the science of biology that enables technology Biotechnology harnesses the power of the biomolecular and cellular processes to create products and technologies that enhance our lives and the wellbeing of the planet. Biotechnology has been utilizing microorganisms' biological processes for over six thousand years to create useful food items like cheese and bread as well as to keep dairy products in good condition.
Modern biotechnology has created breakthrough products and technology to treat rare and debilitating illnesses help reduce our footprint on the environment and feed hungry people, consume less energy and use less and provide safer, more clean and productive industrial production processes.
Biotechnology is credited with groundbreaking advancements in technological development and development of products to create sustainable and cleaner world. This is in large part due to biotechnology that we've made progress toward the creation of more efficient industrial manufacturing bases. Additionally, it assists in the creation of greener energy, feeding more hungry people and not leaving a large environmental footprint, and helping humanity fight rare and fatal diseases.
Our writing services for assignments within the field of biotechnology covers all kinds of subjects that are designed to test and validate the skills of students prior to awarding their certificates. We assist students to successfully complete their course in all kinds of biotechnology-related courses. This includes biological sciences for medical use (red) and eco-biotechnology (green) marine biotechnology (blue) and industrial biotechnology (white).
Our primary goal in preparing this list of the top 100 biotechnology assignment subjects is to aid students in deciding on effective time management techniques. We've witnessed a large amount of cases where when looking for online help with assignments with the topic, examining sources of information, and citing the correct order of reference students find themselves stuck at various points. In the majority of cases, students have difficulty even to get through their dilemma of choosing a topic. This is why we contribute in our effort to help make the process easier for students in biotech quickly and efficiently. Our students are able to save time and energy in order to help them make use of the time they are given to write the assignment with the most appropriate topics.
Let's look at some of the newest areas of biotechnology research and the related areas.
A variety of studies are being conducted into the techniques used by pathogens in order to infect humans and other species and for designing strategies for countering the disease. The main areas that are available to study by biotech researchers include:
Another significant area for research in biotechnology for plants is to study the genetic causes of the plant's responses to scarcity and salinity, which have a significant impact on yields of the crop and food.
It's also a significant area for conducting research in biotechnology. One of the most important reasons for doing so could be the identification of various genetic factors that cause differences in drug effectiveness and susceptibility for adverse reactions. Some of the subjects which can be studied are,
A further area of research in biotechnology research is the study of the genetic diversity of humans for its applications in criminal justice. Some of the topics that could be studied include,
It is possible to conduct research in order to create innovative methods and processes in the fields of food processing and water. The most fascinating topics include:
This topic includes high-resolution protein expression profiling for the investigation of proteome profiles. The following are a few of the most fascinating topics:
This is an additional aspect of biotechnology research. The current trend is to discover new methods to combat cancer. Bioinformatics may help identify proteins and genes as well as their role in the fight against cancer. Check out some of the areas that are suitable to study.
This is a fascinating aspect of biotechnology, which can be used to identify effective tools to address the most serious health issues.
We've prepared a list of the top 100 most suggested dissertation topics, which were compiled by our experts in research. They've made sure to offer a an extensive list of topics that cover all aspects of the topic. We hope that this list will meet all of the requirements for assistance with your dissertation . Let us start with our list of subjects, one at a time each one
We attempted to cover the essential topics needed for research work. Other topics are available that could be picked based on our interests, the facilities available and resources available for the research, as well as resources and time limits.
We have reached the end of this list. We feel it was beneficial in satisfying the selection criteria. Furthermore, the inclusion of biotechnology-related assignment themes was done in such a manner that they may help us with the requirements of assignment writing kinds and forms. The themes listed above can meet our demands for topic selection linked to aid with case studies and essay assistance, research paper writing help , or thesis writing help .
What are some biotechnology research proposal topics .
Some of biotechnology topics are:
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A thesis for Distinction in Biology is a wonderful way for you to close the loop on your undergraduate research experience and showcase your scientific scholarship. Your thesis will be evaluated by the Faculty in Biology and answers the following questions: What did you do? Why did you do it? What is the significance of your results? What else would you do, were you to continue the project?
In answering the above questions, you have an opportunity to demonstrate your understanding and intellectual ownership of a project; not simply your productivity in the lab. The volume of results or completeness of the study is not critical for a successful thesis. Instead, we will be looking for the following:
Expanded guidelines can be found in the Biology Thesis Assessment Protocol (BioTAP):
The basic format of the thesis should resemble that of any scientific journal article that is common in your subdiscipline. It generally includes the following sections: Introduction & Background; Methods; Results; Discussion; Acknowledgements; and References. In some instances, it may be useful to sub-divide the Methods & Results section to correspond to multiple aims. However, if you chose to take this route, remember that there should still be a general Introduction and Discussion sections that address the project as a whole. The thesis should not consist of several "mini-papers" that are unconnected.
The format of the final copy should follow these guidelines:
Sample Theses
Examples of Distinction papers from previous years are available for examination in the Undergraduate Studies Office (Rm 135 BioSci). Several samples are also available below as PDF files.
Additional Resources
A thesis statement portrays the central idea of your research paper or essay. Not everyone is an expert at writing a coherent, well-structured thesis statement, so they need assistance from reliable websites to find a strong thesis statement for their essay. Before writing a statement for a subject like biotechnology, you must do a little homework beforehand. To ease the process, we have written down 31 biotechnology thesis statement that can help you compile a perfect research paper.
Respiratory viruses are the leading cause of mortality in children. As viruses can mutate easily, it becomes difficult to carry out clinical trials. Dealing with emerging viruses has always remained a high-alert task.
CRISPR-Cas-based editing of rice genomes opens up opportunities in the development of commercial crop plants. Various steps under controlled conditions are carried out for the genome editing process, which includes planning, vector construction, the transformation of plants, screening at the molecular level, plant phenotyping, and field trials.
Protection of grapevine from viruses is unavoidable. Therefore, such strategies need to be adopted that provide a habitat for the least dangerous viral strains to co-exist with the plants without causing notable harm to the crops.
Breast cancer screening at regular intervals is crucial to receiving an early diagnosis of the disease. Once the tumour enters the bloodstream, it can spread rapidly and damage other organs quickly. A delayed diagnosis might lead to distant metastases and a poor prognosis.
Excessive use of antibiotics to treat skin-related issues can do more harm than good. It is critical to emphasise the risks of antibiotic overprescription, as it kills good bacteria and results in the expansion of antibiotic-resistant strains, thus disturbing the body’s largest organ microbiome.
Jatropha curcas L. is used as the feedstock in the production of biodiesel. Techniques such as in-vitro plant propagation, somatic embryogenesis, gene transformation studies, production of haploids, and development of elite germplasm are required to upscale its biomass availability globally.
Several antibody therapies are already known to prevent HIV infection, but the production of other therapeutic antibodies and proteins using plant biotechnology reduces the overall cost of the system. Compared to bioreactor-based processes, this system requires less money to produce strong anti-HIV antibodies.
One of the important tools of biotechnology used to control environmental pollution is white rot fungi (WRFs). Using mycoremediation, WRF degrades the lignin using its mycelia. The mycelium punctures the cell cavity and allows the ligninolytic enzymes (LEM) to release, which then forms the sponge-like mass in white color.
High quantities of phenol in the industrial waste can be hazardous to living organisms. The P. rhodesiae KCM-R5 bacterium can make biofilm and is capable of degrading phenol and its derivatives by using phenol in its metabolism. Therefore, engineered PEO cryogel-P. rhodesiae KCM R5 biofilms can be used to treat industrial wastewater detoxification.
Cinnamomum cassia is a valuable medicinal herb with anti-cancer and antioxidant properties. Fermenting the cinnamon with Lactobacillus Plantarum enhances the phenolic compounds and flavonoids, subsequently improving the plants’ anti-cancer and antioxidant capabilities.
The human pathogen L. monocytogenes is a potential organism to carry out bioremediation. It is a solvent-tolerant organism that secretes solvent-stable lipase that can readily break down polyester plastic and lipids in wastewater streams.
Salinity stress is one of the main abiotic factors that restrict crop growth. Plant growth in saline environments can be improved by using Bacillus safensis PM22 as a bio-inoculant or biofertilizer. This PGPR can increase photosynthetic efficiency, antioxidant levels, osmoprotectant synthesis, and decreased oxidative stress markers.
Peptic ulcer disease is commonly caused by H. pylori infection and aspirin use. Using antibiotics with L. reuteri probiotics is beneficial which causes the good bacteria to serve as ulcer biotherapy, promoting mucus secretion, reducing the size of ulcer and the number of pathogens in the body.
To improve the sense-response function, a quick transformation of biosensors using an abscisic acid receptor obtained from a plant PYR1 (Pyrabactin Resistance 1), which binds to a malleable binding pocket, is needed. It is required to heterodimerize a ligand.
The amount of total mRNA expressed in a cell is essential to determine the clinical outcomes of the cells using tumor phenotypes. Intra-tumor genetic heterogeneity, altered genes, and trends in metabolic dysfunction impact the total mRNA expression (TmS) by cancer-specific marking.
Unlike conventional DdCBEs that result in undesirable off-target conversions of C-to-T in mitochondrial DNA (mtDNA) of humans, the whole sequencing of the mitochondrial genome shows HiFi-DdCBEs are extremely precise and structured. This system keeps off-target mutations away, thus resulting in the efficient application of therapeutic treatments.
With the help of a detection technique called fluorescence anisotropy in molecular biotechnology, the development of macromolecules can be studied using the changes in their rotational potency. STARSS (selective time-resolved anisotropy with reversibly switchable states) is used to improve the limitations of this system as it can probe large structures, which helps in studying the whole proteome of a human.
Conventional organoid culture can be replaced with the engineered approach that transforms single injections of stem cells into arrays of structures similar to organs in a dish. This system is scalable and enables the growth and expansion of organoids, so it can be continued without passaging.
An application of transgenic plant biotechnology results in the production of consumable oral vaccines. The purpose can be achieved by using a glycoprotein gene (G-protein) that covers the surface of the rabies virus to be expressed in tomato plants. Transformation of cotyledons is mediated by Agrobacterium tumefaciens in plants.
To produce precise and programmable outcomes, synthetic gene circuits with multiple input signals that can be customized has been used. The system can be employed to study unrealized traits of plants and precisely constructed programs related to the process of transcription in cells.
To yield the substrate of an inducible enzyme, i.e., tannase, Citrus limetta peels can be used. This is a useful study as milk production and growth rates of animals are enhanced with the help of tannase, which degrades the tannin, thus producing gallic acid and glucose. The research further points toward low tannin-based animal feed at the industrial level.
Kidney diseases lead to obesity. The study shows the use of two different strains of Lactobacillus to improve kidney insufficiency and metabolic disorder, which is associated with obesity. A combination of Lactobacillus strains (Pro1 + Pro2) as a supplement of various juices and milk is essential for lowering obesity-associated kidney diseases.
To protect the cotton from the most destructive pest, i.e., the Pink Bollworm ( Pectinophora gossypiella ), a host plant resistance technique is needed. Large-scale cultivation can be protected using eco-friendly Bt -resistance. The growth of non- Bt crops helps control the Pink Bollworm.
Wheat ( Triticum aestivum L. ). is a staple food crop worldwide and can be studied using morphological markers. These markers focus on the detection of specific genes, which are of high interest economically. RAPD and similar molecular techniques can be employed.
The RED LINGZHI MUSHROOM ( Ganodermalucidum ) is an important therapeutic agent that can be used to produce triterpenoids. The effect of potential ultrasonic radiations along with the solvent can be used to study the shortened extraction time and to produce a high yield of triterpenoids from various fruit bodies of G.lucidum.
Dependence on fossil fuels is rising daily to meet energy and chemical feedstock needs. Microbiology plays a significant role in the oil industry via different microbial-induced processes. We can conduct research in the field of microbiology to recover fossil fuel energy resources. However, we will acquire renewable energy sources in the long run as our future economy depends on them.
DNA acts as a blueprint to transcribe genes and proteins to form organs as the cells undergo a differentiation process. Most of these transcriptional changes are physiological, but pathological changes also drive them in abnormal cases. Using transcriptomics and Next-Generation Sequencing, we can study these cellular phenotypes. In the future, we expect to study these techniques in clinical practice.
Industrial biotechnology is blooming as the chemical industry needs chemicals to produce fuels and solvents. Designing and establishing efficient factories to synthesize them is a big challenge. Metabolic engineering is used in the fermentation procedure, and it acquires transcriptome, proteome and metabolome analysis along with mathematical modeling. Moreover, systems biology can improve the cell factory development process.
Erythritol is a popular natural sweetener in the food industry. As the number of diabetes patients grows, so does the demand for lower-calorie foods. It is usually used as a sweetener in calorie-deficient foods. Its synthesis procedure is more challenging as compared to other polyols. It is needed to improve its concentration, productivity, and yield.
A haploid yeast called Blastobotrys adeninivorans is a member of the subphylum Saccharomycotina. It has unusual characteristics, including thermo- and osmo-tolerance. Its genome is completely sequenced, and now many gene manipulations are possible. Therefore, it is a good host for gene expression. In addition, it has multiple applications in industrial biotechnology.
Ageing is the leading cause of death. The slow process of ageing helps to provide many medical benefits. Different genes and pathways play a vital role in regulating the ageing process. Clinical trials address many challenges, ranging from anti-ageing understanding to commercializing anti-ageing products.
After reading all these thesis statement examples , you are now clear about trending topics in the biotech research field. Select the statement you apprehend the most and start writing for a research paper !
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Are You Searching Research Topics For Biotechnology , Topics For Biotechnology Research Paper, Biotechnology Research Topics For Students, Research Topics Ideas For Biotechnology, Biotechnology Research Topics For PhD, Biotechnology PhD Topics. So You are in right place.
In this article, we provide you latest research topics for Biotechnology with a full Phd thesis. By these research topics for Biotechnology you can get idea for your research work. On this website, you can get lots of Biotechnology Research Topics for College Students, PhD, Mphil, Dissertations, Thesis, Project, Presentation, Seminar or Workshop. Check the suggestions below that can help you choose the right research topics for Biotechnology: You can also Free Download Biotechnology Research PhD Thesis in Pdf by the given link.
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Ccds outstanding phd thesis award 2024, congratulations to the following phd graduates for their achievement, for contributions to building generalizable solutions that can enhance the capabilities and applicability of aiot systems..
Dr XU Huatao Building Generalizable Deep Learning Solutions for Mobile Sensing
This thesis signifies a significant leap in mobile sensing with deep learning. It introduces LIMU-BERT, a pioneering sensor foundation model adaptable to various applications, and integrates it into UniHAR, a universal learning framework that trains models across domains using physics-informed data augmentation. A notable innovation is 'Penetrative AI,' the first-ever application of Large Language Models (LLMs) like ChatGPT for processing IoT sensor signals. This breakthrough enables LLMs to interact with the physical world, laying the groundwork for generalizable IoT solutions. The thesis's excellence is recognized by the SenSys 2021 best paper runner-up award and the GetMobile 2022 research highlight. Its models have gained nationwide adoption in Eleme, China's second-largest food delivery service. It also has sparked widespread discussion on social media. Altogether, this work substantially enriches the mobile sensing field, expanding both the scope and effectiveness of AIoT systems in practical applications.
Dr DWIVEDI Vijay Prakash Deep Learning for Graph Structured Data
This thesis marks a significant advancement in deep learning for graph-structured data which are ubiquitous in domains such as drug discovery, social networks, medicine and transportation. Addressing the inadequacies of traditional deep learning approaches for such data, the thesis introduces comprehensive benchmarks for assessing Graph Neural Networks (GNNs) across varied domains. A key contribution is the extension of Transformer networks, fundamental to ChatGPT, to graph domains, integrating graph-based inductive biases and positional encodings, thereby enhancing expressivity and generalization. His work also proposes novel techniques for learning distinct structural and positional representations in GNNs, boosting model capacities. Further, he develops scalable Graph Transformers that can adapt to massive graphs with billions of edge connections, employing efficient local and global graph representations and fast neighborhood sampling. Overall, this thesis paves the way for the application of GNNs in complex real-world relational data scenarios, significantly contributing to the field of graph representation learning.
Dr HU Qinghao Building Efficient and Practical Machine Learning Systems
Emerging ML technologies have empowered transformative applications, such as ChatGPT and Stable Diffusion. These breakthroughs heavily rely on advanced system support, encompassing training frameworks and cluster schedulers. However, as ML workloads proliferate and billion-scale models surface, current systems fail to handle them efficiently. Qinghao’s thesis focuses on addressing efficiency and practicality issues with ML-tailored system designs. His research expands along two lines: (1) Efficiency. He pioneers system optimizations for both cluster and job levels. His ground-breaking work is the first to facilitate hyperparameter tuning for large models such as GPT-3. Through novel model scaling, fusion, and interleaving, he achieves two orders of magnitude acceleration. (2) Practicality. Most existing work targets excellent system performance while ignoring its complexity and usability. Qinghao first attains the state-of-the-art performance under the non-intrusive design principle in cluster scheduling systems. Besides, he crafts a unified framework to achieve transparent, performant and lightweight systems.
Prof Loy Chen Change (Jury Chair)
Assoc Prof Tang Xueyan
Assoc Prof Lam Siew Kei
Assoc Prof Zhang Hanwang
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Theses/Dissertations from 2022. PDF. Regulation of the Heat Shock Response via Lysine Acetyltransferase CBP-1 and in Neurodegenerative Disease in Caenorhabditis elegans, Lindsey N. Barrett. PDF. Determining the Role of Dendritic Cells During Response to Treatment with Paclitaxel/Anti-TIM-3, Alycia Gardner. PDF.
Research Paper 01 Dec 1992. Biological Oxidation of Hydrochlorofluorocarbons (HCFCs) by a Methanotrophic Bacterium ... Nature Biotechnology (Nat Biotechnol) ISSN 1546-1696 (online) ISSN 1087-0156 ...
m.sc biotechnology thesis : "two dimensional polyacrylamide gel electrophoresis of human uterine tissue for detection of proteins" September 2011 DOI: 10.13140/RG.2.2.27453.46564
and growing collection of techniques, grounded in molecular and cell biology, for. analyzing and manipulating the molecular building blocks of life. The term also. designates products, such as ...
Biotechnology Research Paper Topics. This collection of biotechnology research paper topics provides the list of 10 potential topics for research papers and overviews the history of biotechnology. The term biotechnology came into popular use around 1980 and was understood to mean the industrial use of microorganisms to make goods and services ...
Explore a collection of master's theses in molecular and cellular biology from UMass Amherst graduate students.
Dive into the world of 200+ biotechnology research topics, from genetic engg to emerging trends. Explore the future of innovation in all sectors. ... Programming, Projects, Thesis & Research Papers. Follow on social media. For Contribution, Please email us at: editor [at] statanalytica.com ...
In this context, a review paper with current findings on diagnostic tests and vaccine paradigms could speed up future COVID-19 infection containment and prevention studies. Emerging biotechnologies largely contribute to fighting this invisible enemy, COVID-19, and more importantly on fronts of its diagnosis and vaccine development.
Starting in the mid-1980s, biotechnology became a very popular word in the title of research publications, appearing in papers concerning business, industry, biomedicine, chemical engineering, agricultural sciences, and even social sciences (Kennedy, 1991). In short, biotechnology signifies a new biological approach to a wide range of industries.
A Thesis in the Field of Biotechnology Management for the Degree of Master of Liberal Arts in Extension Studies Harvard University . May 2019 . ... fewer of high-profile published research papers are irreproducible (Begley, Buchan, and Dirnagl, 2015). It was also reported in an article in 2016 published by Nature: The
The master's degree programme concludes with a master's thesis of 35 weeks duration that includes a written report and oral presentation. The topic of the thesis can be chosen according to the student's interests in the field of biotechnology. Important: the master's thesis needs to completed in a different group or company department - and ...
Check this list of top 100 biotechnology dissertation topics trending in 2021 recommended by experts at Thoughtful Minds. ... For instance, all our topic selection requirements related to case study help, essay help, research paper writing help or thesis help can also be met with the topics in the above-mentioned list.
Structure for writing a scientific research proposal in biotechnology. The aim or goal and objective of the biotechnology research proposal should give a broad indication of the expected research outcome and the hypothesis to be tested can also be the aim of your study. The objective can be categorized as primary and secondary according to the ...
Follow. Theses/Dissertations from 2024 PDF. Characterization of Cellular Metabolism Regulation by the Transcription Factor Centromere Binding Factor 1 (Cbf1), Spencer Ellsworth Theses/Dissertations from 2023 PDF
A knowledge-based perception analysis about Biotechnology among university students in Bangladesh . Ali, Fariha Fatema (Brac University, 2023-10) Biotechnology is a rapidly evolving field of science. However, the success of this field depends on the acceptance of the research product by the user or consumers.
Search within this Collection: The School of Biological Sciences is a world leading research institution and is committed to communicating the relevance of our research to the public, research sponsors and collaborators and industrial partners. This material is presented to ensure timely dissemination of scholarly and technical work.
3. After the Biology/Biotechnology office has cleared the thesis and any necessary corrections have been made, final copies may be made. 4. After copies are made students should get committee members' signatures. All signature pages must be printed on the same archival paper as the manuscript and all signatures must be original and must
Biotechnology is the use of. technology to use, modi fy or upgrade the p art or whole of biological system for industrial and human. welfare. Biotechnology is defined as: 1) "Biotechnology is ...
Look at some of the top trends in biotech research and recent Biotechnology Topics that are bringing massive changes in this vast world of science, resulting in some innovation in life sciences and biotechnology ideas. Development of vaccine: Development of mRNA has been done since 1989 but has accelerated to combat the pandemic. As per many ...
Furthermore, the inclusion of biotechnology-related assignment themes was done in such a manner that they may help us with the requirements of assignment writing kinds and forms. The themes listed above can meet our demands for topic selection linked to aid with case studies and essay assistance, research paper writing help, or thesis writing help.
The format of the final copy should follow these guidelines: Cover Page (sample): Title; student's name; supervisor's name; date of submission; 3 signature lines at bottom right (Research Supervisor, DUS, Reader). Please follow the format and language of the sample. Abstract Page: single-spaced, roughly 250 words. Thesis should be double-spaced.
To ease the process, we have written down 31 biotechnology thesis statement that can help you compile a perfect research paper. Problems in Clinical Trials for Emerging Respiratory Viruses. Respiratory viruses are the leading cause of mortality in children. As viruses can mutate easily, it becomes difficult to carry out clinical trials.
Research Topic For Biotechnology 2023. Sr. No. Research Topic. Check Thesis. 1. Identification of genetic locus associated with resistance to brown planthopper. Download. 2. Identifying genes expressed during water stress in rice cv Nootripathu roots.
The thesis's excellence is recognized by the SenSys 2021 best paper runner-up award and the GetMobile 2022 research highlight. Its models have gained nationwide adoption in Eleme, China's second-largest food delivery service. It also has sparked widespread discussion on social media. Altogether, this work substantially enriches the mobile ...