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1.
Molecules ; 27(7)2022 Mar 24.
Article in English | MEDLINE | ID: covidwho-1785835

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen and responsible for causing life-threatening infections. The emergence of hypervirulent and multidrug-resistant (MDR) S. aureus strains led to challenging issues in antibiotic therapy. Consequently, the morbidity and mortality rates caused by S. aureus infections have a substantial impact on health concerns. The current worldwide prevalence of MRSA infections highlights the need for long-lasting preventive measures and strategies. Unfortunately, effective measures are limited. In this study, we focus on the identification of vaccine candidates and drug target proteins against the 16 strains of MRSA using reverse vaccinology and subtractive genomics approaches. Using the reverse vaccinology approach, 4 putative antigenic proteins were identified; among these, PrsA and EssA proteins were found to be more promising vaccine candidates. We applied a molecular docking approach of selected 8 drug target proteins with the drug-like molecules, revealing that the ZINC4235426 as potential drug molecule with favorable interactions with the target active site residues of 5 drug target proteins viz., biotin protein ligase, HPr kinase/phosphorylase, thymidylate kinase, UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-L-lysine ligase, and pantothenate synthetase. Thus, the identified proteins can be used for further rational drug or vaccine design to identify novel therapeutic agents for the treatment of multidrug-resistant staphylococcal infection.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Vaccines , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Genomics , Humans , Ligases , Methicillin-Resistant Staphylococcus aureus/genetics , Molecular Docking Simulation , Staphylococcal Infections/prevention & control , Staphylococcus aureus , Vaccinology
2.
Molecules ; 27(7)2022 Apr 06.
Article in English | MEDLINE | ID: covidwho-1776294

ABSTRACT

The continued emergence of human coronaviruses (hCoVs) in the last few decades has posed an alarming situation and requires advanced cross-protective strategies against these pandemic viruses. Among these, Middle East Respiratory Syndrome coronavirus (MERS-CoV), Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), and Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) have been highly associated with lethality in humans. Despite the challenges posed by these viruses, it is imperative to develop effective antiviral therapeutics and vaccines for these human-infecting viruses. The proteomic similarity between the receptor-binding domains (RBDs) among the three viral species offers a potential target for advanced cross-protective vaccine designs. In this study, putative immunogenic epitopes including Cytotoxic T Lymphocytes (CTLs), Helper T Lymphocytes (HTLs), and Beta-cells (B-cells) were predicted for each RBD-containing region of the three highly pathogenic hCoVs. This was followed by the structural organization of peptide- and mRNA-based prophylactic vaccine designs. The validated 3D structures of these epitope-based vaccine designs were subjected to molecular docking with human TLR4. Furthermore, the CTL and HTL epitopes were processed for binding with respective human Lymphocytes Antigens (HLAs). In silico cloning designs were obtained for the prophylactic vaccine designs and may be useful in further experimental designs. Additionally, the epitope-based vaccine designs were evaluated for immunogenic activity through immune simulation. Further studies may clarify the safety and efficacy of these prophylactic vaccine designs through experimental testing against these human-pathogenic coronaviruses.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/prevention & control , Epitopes, B-Lymphocyte , Epitopes, T-Lymphocyte , Humans , Molecular Docking Simulation , Proteomics , RNA, Messenger , Vaccines, Subunit/chemistry , Vaccinology
3.
Science ; 375(6585): 1133-1139, 2022 Mar 11.
Article in English | MEDLINE | ID: covidwho-1736002

ABSTRACT

The vaccine and drug discovery responses to COVID-19 have worked far better than could have been imagined. Yet by the end of 2021, more than 5 million people had died, and the pandemic continues to evolve and rage globally. This Review will describe how each of the vaccines, antibody therapies, and antiviral drugs that have been approved to date were built on decades of investment in technology and basic science. We will caution that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has so far proven a straightforward test of our pandemic preparedness, and we will recommend steps we should undertake now to prepare for, to minimize the effects of, and ideally to prevent future pandemics. Other Reviews in this series describe the interactions of SARS-CoV-2 with the immune system and those therapies that target the host response to infection.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Vaccines , COVID-19/drug therapy , COVID-19/prevention & control , Pandemics/prevention & control , SARS-CoV-2/immunology , Antibodies, Monoclonal/therapeutic use , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Disease Progression , Drug Development , Drug Discovery , Humans , SARS-CoV-2/drug effects , Vaccinology , Viral Vaccines/immunology , Virus Diseases/drug therapy , Virus Diseases/prevention & control
4.
Ther Deliv ; 13(3): 187-203, 2022 03.
Article in English | MEDLINE | ID: covidwho-1709654

ABSTRACT

As SARS-CoV-2 emerge, variants such as Omicron (B.1.1.529), Delta (B.1.617.2), and those from the United Kingdom (B.1.1.7), South Africa (B.1.351), Brazil (P.1) and India (B.1.6.17 lineage) have raised concerns of the reduced neutralising ability of antibodies and increased ability to evade the current six approved COVID-19 vaccine candidates. This viewpoint advocates for countries to conduct prior efficacy studies before they embark on mass vaccination and addresses the role of nanoparticles as carrier vehicles for these vaccines with a view to explore the present challenges and forge a path for a stronger and more viable future for the development of vaccines for SARS-CoV-2 and future pandemics. We also look at the emerging prophylactics and therapeutics in the light of ongoing cases of severe and critical COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Vaccinology
7.
Science ; 375(6576): 22-23, 2022 Jan 07.
Article in English | MEDLINE | ID: covidwho-1636145

ABSTRACT

Correlates and surrogates of desired outcomes are valuable but have limitations.


Subject(s)
Vaccinology
8.
Methods Mol Biol ; 2414: 433-447, 2022.
Article in English | MEDLINE | ID: covidwho-1588848

ABSTRACT

Vaccines induce a highly complex immune reaction in secondary lymphoid organs to generate immunological memory against an antigen or antigens of interest. Measurement of post immunization immune responses generated by specialized lymphocyte subsets requires time-dependent sampling, usually of the blood. Several T and B cell subsets are involved in the reaction, including CD4 and CD8 T cells, T follicular helper cells (Tfh), and germinal center B cells alongside their circulating (c) counterparts; cTfh and antibody secreting cells. Multicolor flow cytometry of peripheral blood mononuclear cells (PBMC) coupled with high-dimensional analysis offers an opportunity to study these cells in detail. Here we demonstrate a method by which such data can be generated and analysed using software that renders multidimensional data on a two dimensional map to identify rare vaccine-induced T and B cell subsets.


Subject(s)
Flow Cytometry , Leukocytes, Mononuclear , Data Analysis , T-Lymphocytes, Helper-Inducer , Vaccinology
10.
Pan Afr Med J ; 38: 313, 2021.
Article in English | MEDLINE | ID: covidwho-1547767

ABSTRACT

For 15 years, the Annual African Vaccinology Course (AAVC) hosted by the Vaccines for Africa Initiative, has been at the forefront of vaccinology training in Africa. The AAVC was developed in 2005 in response to the growing demand for vaccinology training in Africa. To date, 958 policy makers, immunization managers, public and private health practitioners, scientists, postgraduate and postdoctoral students have been trained. These participants are from 44 of the 54 African countries. The course content covers diverse topics such as considerations for new vaccine introduction, mathematical modelling, and emerging and re-emerging vaccine preventable diseases. As the landscape of vaccinology continues to evolve, the AAVC aims to expand the reach of vaccinology training using blended learning approaches which will incorporate online and face-to-face formats, while expanding access to this popular course. Ultimately, the AAVC endeavours to develop a big pool of vaccinology expertise in Africa and to strengthen regional ownership for immunization programmes.


Subject(s)
Vaccination/methods , Vaccines/administration & dosage , Vaccinology/education , Africa , Humans , Immunization Programs/organization & administration , Vaccine-Preventable Diseases/prevention & control
12.
Methods Mol Biol ; 2414: 1-16, 2022.
Article in English | MEDLINE | ID: covidwho-1516809

ABSTRACT

Reverse vaccinology (RV) is the state-of-the-art vaccine development strategy that starts with predicting vaccine antigens by bioinformatics analysis of the whole genome of a pathogen of interest. Vaxign is the first web-based RV vaccine prediction method based on calculating and filtering different criteria of proteins. Vaxign-ML is a new Vaxign machine learning (ML) method that predicts vaccine antigens based on extreme gradient boosting with the advance of new technologies and cumulation of protective antigen data. Using a benchmark dataset, Vaxign-ML showed superior performance in comparison to existing open-source RV tools. Vaxign-ML is also implemented within the web-based Vaxign platform to support easy and intuitive access. Vaxign-ML is also available as a command-based software package for more advanced and customizable vaccine antigen prediction. Both Vaxign and Vaxign-ML have been applied to predict SARS-CoV-2 (cause of COVID-19) and Brucella vaccine antigens to demonstrate the integrative approach to analyze and select vaccine candidates using the Vaxign platform.


Subject(s)
Machine Learning , Vaccines , Vaccinology , Brucella Vaccine , COVID-19 , COVID-19 Vaccines , Computational Biology , Humans
13.
Immunogenetics ; 73(6): 459-477, 2021 12.
Article in English | MEDLINE | ID: covidwho-1427234

ABSTRACT

Since 2019, the world was involved with SARS-CoV-2 and consequently, with the announcement by the World Health Organization that COVID-19 was a pandemic, scientific were an effort to obtain the best approach to combat this global dilemma. The best way to prevent the pandemic from spreading further is to use a vaccine against COVID-19. Here, we report the design of a recombinant multi-epitope vaccine against the four proteins spike or crown (S), membrane (M), nucleocapsid (N), and envelope (E) of SARS-CoV-2 using immunoinformatics tools. We evaluated the most antigenic epitopes that bind to HLA class 1 subtypes, along with HLA class 2, as well as B cell epitopes. Beta-defensin 3 and PADRE sequence were used as adjuvants in the structure of the vaccine. KK, GPGPG, and AAY linkers were used to fuse the selected epitopes. The nucleotide sequence was cloned into pET26b(+) vector using restriction enzymes XhoI and NdeI, and HisTag sequence was considered in the C-terminal of the construct. The results showed that the proposed candidate vaccine is a 70.87 kDa protein with high antigenicity and immunogenicity as well as non-allergenic and non-toxic. A total of 95% of the selected epitopes have conservancy with similar sequences. Molecular docking showed a strong binding between the vaccine structure and tool-like receptor (TLR) 7/8. The docking, molecular dynamics, and MM/PBSA analysis showed that the vaccine established a stable interaction with both structures of TLR7 and TLR8. Simulation of immune stimulation by this vaccine showed that it evokes immune responses related to humoral and cellular immunity.


Subject(s)
COVID-19 Vaccines/immunology , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/immunology , SARS-CoV-2/immunology , Amino Acid Sequence , Base Sequence , COVID-19/prevention & control , COVID-19 Vaccines/genetics , COVID-19 Vaccines/metabolism , Computational Biology , Epitopes, B-Lymphocyte/chemistry , Epitopes, B-Lymphocyte/genetics , Epitopes, T-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/genetics , HLA Antigens/immunology , Humans , Immunogenicity, Vaccine , Molecular Docking Simulation , Molecular Dynamics Simulation , Molecular Weight , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , Toll-Like Receptor 7/chemistry , Toll-Like Receptor 8/chemistry , Vaccines, Subunit/genetics , Vaccines, Subunit/immunology , Vaccines, Subunit/metabolism , Vaccinology , Viral Proteins/chemistry , Viral Proteins/genetics , Viral Proteins/immunology
14.
Sci Rep ; 11(1): 17626, 2021 09 02.
Article in English | MEDLINE | ID: covidwho-1392887

ABSTRACT

Antigen identification is an important step in the vaccine development process. Computational approaches including deep learning systems can play an important role in the identification of vaccine targets using genomic and proteomic information. Here, we present a new computational system to discover and analyse novel vaccine targets leading to the design of a multi-epitope subunit vaccine candidate. The system incorporates reverse vaccinology and immuno-informatics tools to screen genomic and proteomic datasets of several pathogens such as Trypanosoma cruzi, Plasmodium falciparum, and Vibrio cholerae to identify potential vaccine candidates (PVC). Further, as a case study, we performed a detailed analysis of the genomic and proteomic dataset of T. cruzi (CL Brenner and Y strain) to shortlist eight proteins as possible vaccine antigen candidates using properties such as secretory/surface-exposed nature, low transmembrane helix (< 2), essentiality, virulence, antigenic, and non-homology with host/gut flora proteins. Subsequently, highly antigenic and immunogenic MHC class I, MHC class II and B cell epitopes were extracted from top-ranking vaccine targets. The designed vaccine construct containing 24 epitopes, 3 adjuvants, and 4 linkers was analysed for its physicochemical properties using different tools, including docking analysis. Immunological simulation studies suggested significant levels of T-helper, T-cytotoxic cells, and IgG1 will be elicited upon administration of such a putative multi-epitope vaccine construct. The vaccine construct is predicted to be soluble, stable, non-allergenic, non-toxic, and to offer cross-protection against related Trypanosoma species and strains. Further, studies are required to validate safety and immunogenicity of the vaccine.


Subject(s)
Computational Biology/methods , Vaccines/immunology , Vaccinology/methods , Bacterial Vaccines/immunology , Chagas Disease/immunology , Chagas Disease/prevention & control , Cholera/immunology , Cholera/prevention & control , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/immunology , Humans , Malaria, Falciparum/immunology , Malaria, Falciparum/prevention & control , Plasmodium falciparum/immunology , Protozoan Vaccines/immunology , Trypanosoma cruzi/immunology , Vibrio cholerae/immunology
15.
Vaccine ; 39(37): 5233-5239, 2021 08 31.
Article in English | MEDLINE | ID: covidwho-1347849

ABSTRACT

Modern vaccinology has experienced major conceptual and technological advances over the past 30 years. These include atomic-level structures driving immunogen design, new vaccine delivery methods, powerful adjuvants, and novel animal models. In addition, utilizing advanced assays to learn how the immune system senses a pathogen and orchestrates protective immunity has been critical in the design of effective vaccines and therapeutics. The National Institute of Allergy and Infectious Diseases of the National Institutes of Health convened a workshop in September 2020 focused on next generation assays for vaccine development (Table 1). The workshop focused on four critical pathogens: severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and human immunodeficiency virus (HIV)-which have no licensed vaccines-and tuberculosis (TB) and influenza-both of which are in critical need of improved vaccines. The goal was to share progress and lessons learned, and to identify any commonalities that can be leveraged to design vaccines and therapeutics.


Subject(s)
COVID-19 , Tuberculosis , Animals , Humans , Laboratories , SARS-CoV-2 , Tuberculosis/prevention & control , United States , Vaccinology
16.
Methods ; 195: 120-127, 2021 11.
Article in English | MEDLINE | ID: covidwho-1337009

ABSTRACT

This review discusses the philosophical foundations of what used to be called "the scientific method" and is nowadays often known as the scientific attitude. It used to be believed that scientific theories and methods aimed at the truth especially in the case of physics, chemistry and astronomy because these sciences were able to develop numerous scientific laws that made it possible to understand and predict many physical phenomena. The situation is different in the case of the biological sciences which deal with highly complex living organisms made up of huge numbers of constituents that undergo continuous dynamic processes; this leads to novel emergent properties in organisms that cannot be predicted because they are not present in the constituents before they have interacted with each other. This is one of the reasons why there are no universal scientific laws in biology. Furthermore, all scientific theories can only achieve a restricted level of predictive success because they remain valid only under the limited range of conditions that were used for establishing the theory' in the first place. Many theories that used to be accepted were subsequently shown to be false, demonstrating that scientific theories always remain tentative and can never be proven beyond and doubt. It is ironical that as scientists have finally accepted that approximate truths are perfectly adequate and that absolute truth is an illusion, a new irrational sociological phenomenon called Post-Truth conveyed by social media, the Internet and fake news has developed in the Western world that is convincing millions of people that truth simply does not exist. Misleading information is circulated with the intention to deceive and science denialism is promoted by denying the remarkable achievements of science and technology during the last centuries. Although the concept of intentional design is widely used to describe the methods that biologists use to make discoveries and inventions, it will be argued that the term is not appropriate for explaining the appearance of life on our planet nor for describing the scientific creativity of scientific investigators. The term rational for describing the development of new vaccines is also unjustified. Because the analysis of the COVID-19 pandemic requires contributions from biomedical and psycho-socioeconomic sciences, one scientific method alone would be insufficient for combatting the pandemic.


Subject(s)
Biological Science Disciplines/methods , COVID-19/prevention & control , Concept Formation , Research Design , Vaccinology/methods , Biological Science Disciplines/trends , COVID-19/epidemiology , COVID-19/genetics , Humans , Research Design/trends , Vaccinology/trends
17.
Immunity ; 54(8): 1636-1651, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1336544

ABSTRACT

The development of effective vaccines to combat infectious diseases is a complex multi-year and multi-stakeholder process. To accelerate the development of vaccines for coronavirus disease 2019 (COVID-19), a novel pathogen emerging in late 2019 and spreading globally by early 2020, the United States government (USG) mounted an operation bridging public and private sector expertise and infrastructure. The success of the endeavor can be seen in the rapid advanced development of multiple vaccine candidates, with several demonstrating efficacy and now being administered around the globe. Here, we review the milestones enabling the USG-led effort, the methods utilized, and ensuing outcomes. We discuss the current status of COVID-19 vaccine development and provide a perspective for how partnership and preparedness can be better utilized in response to future public-health pandemic emergencies.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/epidemiology , COVID-19/prevention & control , Research , SARS-CoV-2/immunology , Bioengineering , Biotechnology , COVID-19 Vaccines/administration & dosage , Humans , Models, Molecular , Outcome Assessment, Health Care , Public Health Surveillance , Research/statistics & numerical data , Research/trends , United States/epidemiology , Vaccination Coverage/statistics & numerical data , Vaccinology
18.
Nature ; 597(7874): 97-102, 2021 09.
Article in English | MEDLINE | ID: covidwho-1309448

ABSTRACT

An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape1-3, have activity against diverse sarbecoviruses4-7, and be highly protective through viral neutralization8-11 and effector functions12,13. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E128) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics.


Subject(s)
Broadly Neutralizing Antibodies/immunology , COVID-19/virology , Cross Reactions/immunology , Immune Evasion , SARS-CoV-2/classification , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Adult , Aged , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Antibodies, Viral/chemistry , Antibodies, Viral/immunology , Antibody Affinity , Broadly Neutralizing Antibodies/chemistry , COVID-19/drug therapy , COVID-19/immunology , COVID-19 Vaccines/chemistry , COVID-19 Vaccines/immunology , Cell Line , Cricetinae , Epitopes, B-Lymphocyte/chemistry , Epitopes, B-Lymphocyte/genetics , Epitopes, B-Lymphocyte/immunology , Female , Humans , Immune Evasion/genetics , Immune Evasion/immunology , Male , Mesocricetus , Middle Aged , Models, Molecular , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccinology
19.
Nature ; 596(7872): 410-416, 2021 08.
Article in English | MEDLINE | ID: covidwho-1305364

ABSTRACT

The emergency use authorization of two mRNA vaccines in less than a year from the emergence of SARS-CoV-2 represents a landmark in vaccinology1,2. Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers who were vaccinated with the Pfizer-BioNTech mRNA vaccine (BNT162b2). Vaccination resulted in the robust production of neutralizing antibodies against the wild-type SARS-CoV-2 (derived from 2019-nCOV/USA_WA1/2020) and, to a lesser extent, the B.1.351 strain, as well as significant increases in antigen-specific polyfunctional CD4 and CD8 T cells after the second dose. Booster vaccination stimulated a notably enhanced innate immune response as compared to primary vaccination, evidenced by (1) a greater frequency of CD14+CD16+ inflammatory monocytes; (2) a higher concentration of plasma IFNγ; and (3) a transcriptional signature of innate antiviral immunity. Consistent with these observations, our single-cell transcriptomics analysis demonstrated an approximately 100-fold increase in the frequency of a myeloid cell cluster enriched in interferon-response transcription factors and reduced in AP-1 transcription factors, after secondary immunization. Finally, we identified distinct innate pathways associated with CD8 T cell and neutralizing antibody responses, and show that a monocyte-related signature correlates with the neutralizing antibody response against the B.1.351 variant. Collectively, these data provide insights into the immune responses induced by mRNA vaccination and demonstrate its capacity to prime the innate immune system to mount a more potent response after booster immunization.


Subject(s)
Adaptive Immunity , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Immunity, Innate , T-Lymphocytes/immunology , Vaccinology , Adult , Aged , Antibodies, Neutralizing/immunology , Autoantibodies/immunology , COVID-19 Vaccines/administration & dosage , Female , Humans , Immunization, Secondary , Male , Middle Aged , Single-Cell Analysis , Spike Glycoprotein, Coronavirus/immunology , Transcription, Genetic , Transcriptome/genetics , Young Adult
20.
Viruses ; 13(5)2021 04 28.
Article in English | MEDLINE | ID: covidwho-1302473

ABSTRACT

One of the most effective strategies for eliminating new and emerging infectious diseases is effective immunization. The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) warrants the need for a maximum coverage vaccine. Moreover, mutations that arise within the virus have a significant impact on the vaccination strategy. Here, we built a comprehensive in silico workflow pipeline to identify B-cell- and T-cell-stimulating antigens of SARS-CoV-2 viral proteins. Our in silico reverse vaccinology (RV) approach consisted of two parts: (1) analysis of the selected viral proteins based on annotated cellular location, antigenicity, allele coverage, epitope density, and mutation density and (2) analysis of the various aspects of the epitopes, including antigenicity, allele coverage, IFN-γ induction, toxicity, host homology, and site mutational density. After performing a mutation analysis based on the contemporary mutational amino acid substitutions observed in the viral variants, 13 potential epitopes were selected as subunit vaccine candidates. Despite mutational amino acid substitutions, most epitope sequences were predicted to retain immunogenicity without toxicity and host homology. Our RV approach using an in silico pipeline may potentially reduce the time required for effective vaccine development and can be applicable for vaccine development for other pathogenic diseases as well.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/virology , SARS-CoV-2/immunology , Antigens, Viral/chemistry , Antigens, Viral/immunology , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/immunology , Humans , Immunogenicity, Vaccine , Molecular Docking Simulation , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Subunit/immunology , Vaccinology/methods , Viral Proteins/genetics , Viral Proteins/immunology
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