Immunoinformatics and Structural Analysis for Identification of Immunodominant Epitopes in SARS-CoV-2 as Potential Vaccine Targets

A new coronavirus infection, COVID-19, has recently emerged, and has caused a global pandemic along with an international public health emergency. Currently, no licensed vaccines are available for COVID-19. The identification of immunodominant epitopes for both B- and T-cells that induce protective responses in the host is crucial for effective vaccine design. Computational prediction of potential epitopes might significantly reduce the time required to screen peptide libraries as part of emergent vaccine design. In our present study, we used an extensive immunoinformatics-based approach to predict conserved immunodominant epitopes from the proteome of SARS-CoV-2. Regions from SARS-CoV-2 protein sequences were defined as immunodominant, based on the following three criteria regarding B- and T-cell epitopes: (i) they were both mapped, (ii) they predicted protective antigens, and (iii) they were completely identical to experimentally validated epitopes of SARS-CoV. Further, structural and molecular docking analyses were performed in order to understand the binding interactions of the identified immunodominant epitopes with human major histocompatibility complexes (MHC). Our study provides a set of potential immunodominant epitopes that could enable the generation of both antibody- and cell-mediated immunity. This could contribute to developing peptide vaccine-based adaptive immunotherapy against SARS-CoV-2 infections and prevent future pandemic outbreaks.

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Immune responses of seven different “promiscuous” T-cell epitopes on chimeric peptide vaccine design

Peptides ◽

10.1007/978-94-011-0683-2_242 ◽

1994 ◽

pp. 732-733 ◽

Cited By ~ 2

Author(s):

A. M. DiGeorge ◽

B. Wang ◽

S. F. Kobs-Conrad ◽

P. T. P. Kaumaya

Keyword(s):

T Cell ◽

Immune Responses ◽

Peptide Vaccine ◽

Vaccine Design ◽

T Cell Epitopes ◽

Chimeric Peptide

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Development of Peptide Vaccines in Dengue

Current Pharmaceutical Design ◽

10.2174/1381612823666170913163904 ◽

2018 ◽

Vol 24 (11) ◽

pp. 1157-1173 ◽

Cited By ~ 6

Author(s):

Kavita Reginald ◽

Yanqi Chan ◽

Magdalena Plebanski ◽

Chit Laa Poh

Keyword(s):

T Cell ◽

Neutralizing Antibodies ◽

Peptide Vaccine ◽

Human Leukocyte ◽

Cost Effective ◽

Cell Mediated Immunity ◽

T Cell Epitopes ◽

Peptide Vaccines ◽

Dengue Vaccine ◽

Region Data

Dengue is one of the most important arboviral infections worldwide, infecting up to 390 million people and causing 25,000 deaths annually. Although a licensed dengue vaccine is available, it is not efficacious against dengue serotypes that infect people living in South East Asia, where dengue is an endemic disease. Hence, there is an urgent need to develop an efficient dengue vaccine for this region. Data from different clinical trials indicate that a successful dengue vaccine must elicit both neutralizing antibodies and cell mediated immunity. This can be achieved by designing a multi-epitope peptide vaccine comprising B, CD8+ and CD4+ T cell epitopes. As recognition of T cell epitopes are restricted by human leukocyte antigens (HLA), T cell epitopes which are able to recognize several major HLAs will be preferentially included in the vaccine design. While peptide vaccines are safe, biocompatible and cost-effective, it is poorly immunogenic. Strategies to improve its immunogenicity by the use of long peptides, adjuvants and nanoparticle delivery mechanisms are discussed.

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Attenuated Subcomponent Vaccine Design Targeting the SARS-CoV-2 Nucleocapsid Phosphoprotein RNA Binding Domain: In Silico Analysis

Journal of Immunology Research ◽

10.1155/2020/2837670 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Onyeka S. Chukwudozie ◽

Rebecca C. Chukwuanukwu ◽

Onyekachi O. Iroanya ◽

Daniel M. Eze ◽

Vincent C. Duru ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

In Silico ◽

Rna Binding ◽

Peptide Vaccine ◽

In Silico Analysis ◽

Dynamics Simulation ◽

Effective Vaccine ◽

Translation Efficiency ◽

T Cell Epitopes

The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has previously never been identified with humans, thereby creating devastation in public health. The need for an effective vaccine to curb this pandemic cannot be overemphasized. In view of this, we designed a subcomponent antigenic peptide vaccine targeting the N-terminal (NT) and C-terminal (CT) RNA binding domains of the nucleocapsid protein that aid in viral replication. Promising antigenic B cell and T cell epitopes were predicted using computational pipelines. The peptides “RIRGGDGKMKDL” and “AFGRRGPEQTQGNFG” were the B cell linear epitopes with good antigenic index and nonallergenic property. Two CD8+ and Three CD4+ T cell epitopes were also selected considering their safe immunogenic profiling such as allergenicity, antigen level conservancy, antigenicity, peptide toxicity, and putative restrictions to a number of MHC-I and MHC-II alleles. With these selected epitopes, a nonallergenic chimeric peptide vaccine incapable of inducing a type II hypersensitivity reaction was constructed. The molecular interaction between the Toll-like receptor-5 (TLR5) which was triggered by the vaccine was analyzed by molecular docking and scrutinized using dynamics simulation. Finally, in silico cloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing the pET-28a vector. This research, therefore, provides a guide for experimental investigation and validation.

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Identification of highly conserved, serotype-specific dengue virus sequences: implications for vaccine design

BMC Genomics ◽

10.1186/s12864-019-6311-z ◽

2019 ◽

Vol 20 (S9) ◽

Cited By ~ 2

Author(s):

Li Chuin Chong ◽

Asif M. Khan

Keyword(s):

T Cell ◽

Dengue Virus ◽

Large Scale ◽

Target Selection ◽

Vaccine Design ◽

Effective Vaccine ◽

Amino Acid Difference ◽

Specific Response ◽

T Cell Epitopes ◽

Vaccine Target

Abstract Background The sequence diversity of dengue virus (DENV) is one of the challenges in developing an effective vaccine against the virus. Highly conserved, serotype-specific (HCSS), immune-relevant DENV sequences are attractive candidates for vaccine design, and represent an alternative to the approach of selecting pan-DENV conserved sequences. The former aims to limit the number of possible cross-reactive epitope variants in the population, while the latter aims to limit the cross-reactivity between the serotypes to favour a serotype-specific response. Herein, we performed a large-scale systematic study to map and characterise HCSS sequences in the DENV proteome. Methods All reported DENV protein sequence data for each serotype was retrieved from the NCBI Entrez Protein (nr) Database (txid: 12637). The downloaded sequences were then separated according to the individual serotype proteins by use of BLASTp search, and subsequently removed for duplicates and co-aligned across the serotypes. Shannon’s entropy and mutual information (MI) analyses, by use of AVANA, were performed to measure the diversity within and between the serotype proteins to identify HCSS nonamers. The sequences were evaluated for the presence of promiscuous T-cell epitopes by use of NetCTLpan 1.1 and NetMHCIIpan 3.2 server for human leukocyte antigen (HLA) class I and class II supertypes, respectively. The predicted epitopes were matched to reported epitopes in the Immune Epitope Database. Results A total of 2321 nonamers met the HCSS selection criteria of entropy < 0.25 and MI > 0.8. Concatenating these resulted in a total of 337 HCSS sequences. DENV4 had the most number of HCSS nonamers; NS5, NS3 and E proteins had among the highest, with none in the C and only one in prM. The HCSS sequences were immune-relevant; 87 HCSS sequences were both reported T-cell epitopes/ligands in human and predicted epitopes, supporting the accuracy of the predictions. A number of the HCSS clustered as immunological hotspots and exhibited putative promiscuity beyond a single HLA supertype. The HCSS sequences represented, on average, ~ 40% of the proteome length for each serotype; more than double of pan-DENV sequences (conserved across the four serotypes), and thus offer a larger choice of sequences for vaccine target selection. HCSS sequences of a given serotype showed significant amino acid difference to all the variants of the other serotypes, supporting the notion of serotype-specificity. Conclusion This work provides a catalogue of HCSS sequences in the DENV proteome, as candidates for vaccine target selection. The methodology described herein provides a framework for similar application to other pathogens.

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Attenuated Subcomponent Vaccine Design Targeting the SARS-CoV-2 Nucleocapsid Phosphoprotein RNA Binding Domain: In silico analysis

10.1101/2020.06.30.176537 ◽

2020 ◽

Author(s):

Onyeka S. Chukwudozie ◽

Rebecca C. Chukwuanukwu ◽

Iroanya O. Onyekachi ◽

Eze M. Daniel ◽

Duru C. Vincent ◽

...

Keyword(s):

T Cell ◽

In Silico ◽

Rna Binding ◽

Peptide Vaccine ◽

In Silico Analysis ◽

Dynamics Simulation ◽

Effective Vaccine ◽

Translation Efficiency ◽

T Cell Epitopes ◽

Mhc I

ABSTRACTThe novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has previously never been identified with humans, thereby creating devastation in public health. The need for an effective vaccine to curb this pandemic cannot be overemphasized. In view of this, we, therefore, designed a subcomponent antigenic peptide vaccine targeting the N-terminal (NT) and C-terminal (CT) RNA binding domains of nucleocapsid protein that aid in viral replication. Promising antigenic B-cells and T cell epitopes were predicted using computational pipelines. The peptides “RIRGGDGKMKDL” and “AFGRRGPEQTQGNFG” were the B cell linear epitopes with good antigenic index and non-allergenic property. Two CD8+ and Three CD4+ T-cell epitopes were also selected considering their safe immunogenic profiling such as allergenicity, antigen level conservancy, antigenicity, peptide toxicity, and putative restrictions to a number of MHC-I and II alleles. With these selected epitopes, a non-allergenic chimeric peptide vaccine incapable of inducing a Type II hypersensitivity reaction was constructed. The molecular interaction between the toll-like receptor-5 (TLR5) which was triggered by the vaccine was analyzed by molecular docking and scrutinized using dynamics simulation. Finally, in silico cloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing pET-28a vector. This research, therefore, provides a guide for experimental investigation and validation.

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Sampling SARS-CoV-2 Proteomes for Predicted CD8 T-Cell Epitopes as a Tool for Understanding Immunogenic Breadth and Rational Vaccine Design

Frontiers in Bioinformatics ◽

10.3389/fbinf.2021.622992 ◽

2021 ◽

Vol 1 ◽

Author(s):

Jonathan Hare ◽

David Morrison ◽

Morten Nielsen

Keyword(s):

T Cell ◽

Therapeutic Vaccine ◽

Vaccine Design ◽

Cd8 T Cell ◽

Cell Vaccine ◽

T Cell Epitopes ◽

Global Pandemic ◽

T Cell Vaccine ◽

Rational Vaccine Design ◽

Global And Local

Predictive models for vaccine design have become a powerful and necessary resource for the expeditiousness design of vaccines to combat the ongoing SARS-CoV-2 global pandemic. Here we use the power of these predicted models to assess the sequence diversity of circulating SARS-CoV-2 proteomes in the context of an individual’s CD8 T-cell immune repertoire to identify potential. defined regions of immunogenicity. Using this approach of expedited and rational CD8 T-cell vaccine design, it may be possible to develop a therapeutic vaccine candidate with the potential for both global and local coverage.

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Immune-Informatic Analysis and Design of Peptide Vaccine From Multi-epitopes Against Corynebacterium pseudotuberculosis

Bioinformatics and Biology Insights ◽

10.1177/1177932218755337 ◽

2018 ◽

Vol 12 ◽

pp. 117793221875533 ◽

Cited By ~ 7

Author(s):

Daniela Droppa-Almeida ◽

Elton Franceschi ◽

Francine Ferreira Padilha

Keyword(s):

Tertiary Structure ◽

Peptide Vaccine ◽

Cost Benefit ◽

Corynebacterium Pseudotuberculosis ◽

Effective Vaccine ◽

Amino Acid Residues ◽

Analysis And Design ◽

Bioinformatic Tools ◽

Wide Range ◽

Immunodominant Epitopes

Caseous lymphadenitis (CLA) is a disease caused by Corynebacterium pseudotuberculosis bacteria that affects sheep and goats. The absence of a serologic diagnose is a factor that contributes for the disease dissemination, and due to the formation of granuloma, the treatment is very expensive. Therefore, prophylaxis is the approach with best cost-benefit relation; however, it still lacks an effective vaccine. In this sense, this work seeks to apply bioinformatic tools to design an effective vaccine against CLA, using CP40 protein as standard for the design of immunodominant epitopes, from which a total of 6 sequences were obtained, varying from 10 to 16 amino acid residues. The evaluation of different properties of the vaccines showed that the vaccine is a potent and nonallergenic antigen remaining stable in a wide range of temperatures. The initial tertiary structure of the vaccine was then predicted and a model selected. Later, the process of CP40 protein and TLR2 receptor binding was performed, presenting interaction with this receptor, which plays an important role in the activation of the immune response.

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Multi-epitope Based Peptide Vaccine Design Using Three Structural Proteins (S, E, and M) of SARS-CoV-2: An In Silico Approach

10.1101/2020.06.13.149880 ◽

2020 ◽

Cited By ~ 1

Author(s):

Arpita Singha Roy ◽

Mahafujul Islam Quadery Tonmoy ◽

Atqiya Fariha ◽

Ithmam Hami ◽

Ibrahim Khalil Afif ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Peptide Vaccine ◽

Evolutionary Relationship ◽

Cell Epitope ◽

Epitope Prediction ◽

Vaccine Design ◽

Structural Proteins ◽

T Cell Epitopes ◽

Novel Coronavirus

AbstractSevere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the novel coronavirus responsible for the ongoing pandemic of coronavirus disease (COVID-19). No sustainable treatment option is available so far to tackle such a public health threat. Therefore, designing a suitable vaccine to overcome this hurdle asks for immediate attention. In this study, we targeted for a design of multi-epitope based vaccine using immunoinformatics tools. We considered the structural proteins S, E and, M of SARS-CoV-2, since they facilitate the infection of the virus into host cell and using different bioinformatics tools and servers, we predicted multiple B-cell and T-cell epitopes having potential for the required vaccine design. Phylogenetic analysis provided insight on ancestral molecular changes and molecular evolutionary relationship of S, E, and M proteins. Based on the antigenicity and surface accessibility of these proteins, eight epitopes were selected by various B cell and T cell epitope prediction tools. Molecular docking was executed to interpret the binding interactions of these epitopes and three potential epitopes WTAGAAAYY, YVYSRVKNL, and GTITVEELK were selected for their noticeable higher binding affinity scores −9.1, −7.4, and −7.0 kcal/mol, respectively. Targeted epitopes had 91.09% population coverage worldwide. In summary, we identified three epitopes having the most significant properties of designing the peptide-based vaccine against SARS-CoV-2.

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Scrutinizing surface glycoproteins and poxin-schlafen protein to design a heterologous recombinant vaccine against monkeypox virus

10.1101/2020.01.25.919332 ◽

2020 ◽

Author(s):

Syeda Farjana Hoque ◽

Md. Nazmul Islam Bappy ◽

Anjum Taiebah Chowdhury ◽

Md. Sorwer Alam Parvez ◽

Foeaz Ahmed ◽

...

Keyword(s):

Molecular Docking ◽

Vaccine Development ◽

Peptide Vaccine ◽

Cloning And Expression ◽

Effective Vaccine ◽

Cell Mediated Immunity ◽

Surface Binding ◽

Binding Interaction ◽

Monkeypox Virus ◽

Cell Immunity

AbstractMonkeypox is a zoonotic disease caused by monkeypox virus with noteworthy mortality and morbidity. Several recent outbreaks and the need of dependable reconnaissance have raised the level of concern for this developing zoonosis. In the present study, a reverse vaccinology strategy was developed to construct a peptide vaccine against monkeypox virus by exploring cell surface binding protein, Poxin-Schlafen andenvelope protein. Both humoral and cell mediated immunity induction were the main concerned properties for the designed peptide vaccine. Therefore, both T cell and B cell immunity against monkeypox virus were analyzed from the conserver region of the selected protein. Antigenicity testing, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking approach were used to create the superior epitopes of moneypox virus. The subunit vaccine was constructed using highly immunogenic epitopes with appropriate adjuvant and linkers. Molecular docking examination of the refined vaccine with various MHCs and human immune receptor illustrated higher binding interaction. The designed construct was reverse transcribed and adjusted for E. coli strain K12 earlier to inclusion inside pET28a(+) vector for its heterologous cloning and expression. The study could start in vitro and in vivo studies concerning effective vaccine development against monkeypox virus.

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Sampling SARS-CoV-2 proteomes for predicted CD8 T-cell epitopes as a tool for understanding immunogenic breadth and rational vaccine design

10.1101/2020.08.15.250647 ◽

2020 ◽

Cited By ~ 1

Author(s):

Jonathan Hare ◽

David Morrison ◽

Morten Nielsen

Keyword(s):

T Cell ◽

Therapeutic Vaccine ◽

Vaccine Design ◽

Cd8 T Cell ◽

Cell Vaccine ◽

T Cell Epitopes ◽

Global Pandemic ◽

T Cell Vaccine ◽

Rational Vaccine Design ◽

Global And Local

AbstractPredictive models for vaccine design have become a powerful and necessary resource for the expeditiousness design of vaccines to combat the ongoing SARS-CoV-2 global pandemic. Here we use the power of these predicted models to assess the sequence diversity of circulating SARS-CoV-2 proteomes in the context of an individual’s CD8 T-cell immune repertoire to identify potential. defined regions of immunogenicity. Using this approach of expedited and rational CD8 T-cell vaccine design, it may be possible to develop a therapeutic vaccine candidate with the potential for both global and local coverage.

Download Full-text