Bioinformatic Techniques for Vaccine Development: Epitope Prediction and Structural Vaccinology

2021 ◽  
pp. 413-423
Author(s):  
Peter McCaffrey
Keyword(s):  
Vaccine Development ◽  
Epitope Prediction ◽  
Structural Vaccinology

scholarly journals Immunodominant linear B cell epitopes in the spike and membrane proteins of SARS-CoV-2 identified by immunoinformatics prediction and immunoassay

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kanokporn Polyiam ◽  
Waranyoo Phoolcharoen ◽  
Namphueng Butkhot ◽  
Chanya Srisaowakarn ◽  
Arunee Thitithanyanont ◽  
...  
Keyword(s):  
B Cell ◽  
Cleavage Site ◽  
Vaccine Development ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
E Proteins ◽  
B Cell Epitopes ◽  
C Terminus ◽  
B Cell Epitope ◽  
Linear B

AbstractSARS-CoV-2 continues to infect an ever-expanding number of people, resulting in an increase in the number of deaths globally. With the emergence of new variants, there is a corresponding decrease in the currently available vaccine efficacy, highlighting the need for greater insights into the viral epitope profile for both vaccine design and assessment. In this study, three immunodominant linear B cell epitopes in the SARS-CoV-2 spike receptor-binding domain (RBD) were identified by immunoinformatics prediction, and confirmed by ELISA with sera from Macaca fascicularis vaccinated with a SARS-CoV-2 RBD subunit vaccine. Further immunoinformatics analyses of these three epitopes gave rise to a method of linear B cell epitope prediction and selection. B cell epitopes in the spike (S), membrane (M), and envelope (E) proteins were subsequently predicted and confirmed using convalescent sera from COVID-19 infected patients. Immunodominant epitopes were identified in three regions of the S2 domain, one region at the S1/S2 cleavage site and one region at the C-terminus of the M protein. Epitope mapping revealed that most of the amino acid changes found in variants of concern are located within B cell epitopes in the NTD, RBD, and S1/S2 cleavage site. This work provides insights into B cell epitopes of SARS-CoV-2 as well as immunoinformatics methods for B cell epitope prediction, which will improve and enhance SARS-CoV-2 vaccine development against emergent variants.

Structural Vaccinology: A Three-dimensional View for Vaccine Development

2013 ◽  
Vol 13 (20) ◽  
pp. 2629-2637 ◽  
Author(s):  
Ilaria Ferlenghi ◽  
Roberta Cozzi ◽  
Maria Scarselli
Keyword(s):  
Vaccine Development ◽  
Three Dimensional ◽  
Structural Vaccinology

Computational screening of potential MHC class I restricted cytotoxic T lymphocytes-based common multi-epitopes of major arboviral diseases

2020 ◽  
Vol 15 (8) ◽  
pp. 497-505
Author(s):  
Rakshanda Sajeed ◽  
Kishore Sarma ◽  
Kimmi Sarmah ◽  
Dipankar Biswas ◽  
Biswajyoti Borkakoty
Keyword(s):  
Mhc Class I ◽  
Vaccine Development ◽  
Health Hazard ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Class I ◽  
Population Coverage ◽  
Computational Screening ◽  
Antigenic Properties ◽  
Arboviral Diseases

Aim: Arboviral diseases are a health hazard and Flavivirus and Alphavirus infections are the most common in humans. This study focuses on immunoinformatic approaches to identify potential MHC class I restricted epitopes common for some selected arboviral diseases. Materials & methods: T-cell epitope prediction tool of Immune Epitope Database was employed to identify putative epitopes from the polyproteins of the selected viruses. Further, population coverage, conservancy, antigenic properties and docking analyses were performed to identify potential common epitopes for the selected viruses. Results: Eight common epitopes were screened for the selected viruses based on their population coverage, conservancy, antigenic properties and binding affinity. Conclusion: Considering the in silico potency, identified epitopes may further be subjected for candidate vaccine development against these arboviruses.

scholarly journals Identification, Mapping, and Genetic Diversity of Novel Conserved Cross-Species Epitopes of RhopH2 in Plasmodium knowlesi With Plasmodium vivax

2022 ◽  
Vol 11 ◽  
Author(s):  
Md Atique Ahmed ◽  
Gauspasha Yusuf Deshmukh ◽  
Rehan Haider Zaidi ◽  
Ahmed Saif ◽  
Mohammed Abdulrahman Alshahrani ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Vivax ◽  
Protective Immunity ◽  
Vaccine Development ◽  
Plasmodium Knowlesi ◽  
Epitope Prediction ◽  
Purifying Selection ◽  
Peninsular Malaysia ◽  
Health Concern ◽  
Clinical Samples

Malaria is a major public health concern, and any tangible intervention during the pre-elimination phase can result in a significant reduction in infection rates. Recent studies have reported that antigens producing cross-protective immunity can play an important role as vaccines and halt malaria transmission in different endemic regions. In this study, we studied the genetic diversity, natural selection, and discovered novel conserved epitopes of a high molecular weight rhoptry protein 2 (RhopH2) in clinical samples of Plasmodium knowlesi and Plasmodium vivax cross-protective domains, which has been proven to produce cross-protective immunity in both species. We found low levels of nucleotide diversity (P. knowlesi; π ~ 0.0093, SNPs = 49 and P. vivax π ~ 0.0014, SNPs = 23) in P. knowlesi (n = 40) and P. vivax (n = 65) samples in the PkRhopH2 cross-protective domain. Strong purifying selection was observed for both species (P. knowlesi; dS - dN = 2.41, p < 0.009, P. vivax; dS - dN = 1.58, p < 0.050). In silico epitope prediction in P. knowlesi identified 10 potential epitopes, of which 7 epitopes were 100% conserved within clinical samples. Of these epitopes, an epitope with 10 amino acids (QNSKHFKKEK) was found to be fully conserved within all P. knowlesi and P. vivax clinical samples and 80%–90% conservation within simian malaria ortholog species, i.e., P. coatneyi and P. cynomolgi. Phylogenetic analysis of the PkRhopH2 cross-protective domain showed geographical clustering, and three subpopulations of P. knowlesi were identified of which two subpopulations originated from Sarawak, Malaysian Borneo, and one comprised only the laboratory lines from Peninsular Malaysia. This study suggests that RhopH2 could be an excellent target for cross-protective vaccine development with potential for outwitting strain as well as species-specific immunity. However, more detailed studies on genetic diversity using more clinical samples from both species as well as the functional role of antibodies specific to the novel conserved epitope identified in this study can be explored for protection against infection.

scholarly journals Annotation of Potential Vaccine Targets and Design of a Multi-Epitope Subunit Vaccine against Yersinia pestis through Reverse Vaccinology and Validation through an Agent-Based Modeling Approach

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1327
Author(s):  
Azaz Ul Haq ◽  
Abbas Khan ◽  
Jafar Khan ◽  
Shamaila Irum ◽  
Yasir Waheed ◽  
...  
Keyword(s):  
Immune Response ◽  
Yersinia Pestis ◽  
Vaccine Development ◽  
Dynamic Properties ◽  
Dynamics Simulation ◽  
Strong Immune Response ◽  
Agent Based ◽  
Aliphatic Index ◽  
Structural Vaccinology ◽  
Potential Vaccine

Yersinia pestis is responsible for plague and major pandemics in Asia and Europe. This bacterium has shown resistance to an array of drugs commonly used for the treatment of plague. Therefore, effective therapeutics measurements, such as designing a vaccine that can effectively and safely prevent Y. pestis infection, are of high interest. To fast-track vaccine development against Yersinia pestis, herein, proteome-wide vaccine target annotation was performed, and structural vaccinology-assisted epitopes were predicted. Among the total 3909 proteins, only 5 (rstB, YPO2385, hmuR, flaA1a, and psaB) were shortlisted as essential vaccine targets. These targets were then subjected to multi-epitope vaccine design using different linkers. EAAK, AAY, and GPGPG as linkers were used to link CTL, HTL, and B-cell epitopes, and an adjuvant (beta defensin) was also added at the N-terminal of the MEVC. Physiochemical characterization, such as determination of the instability index, theoretical pI, half-life, aliphatic index, stability profiling, antigenicity, allergenicity, and hydropathy of the ensemble, showed that the vaccine is highly stable, antigenic, and non-allergenic and produces multiple interactions with immune receptors upon docking. In addition, molecular dynamics simulation confirmed the stable binding and good dynamic properties of the vaccine–TLR complex. Furthermore, in silico and immune simulation of the developed MEVC for Y. pestis showed that the vaccine triggered strong immune response after several doses at different intervals. Neutralization of the antigen was observed at the third day of injection. Conclusively, the vaccine designed here for Y. pestis produces an immune response; however, further immunological testing is needed to unveil its real efficacy.

scholarly journals Selecting soluble/foldable protein domains through single-gene or genomic ORF filtering: structure of the head domain of Burkholderia pseudomallei antigen BPSL2063

2015 ◽  
Vol 71 (11) ◽  
pp. 2227-2235 ◽  
Author(s):  
Louise J. Gourlay ◽  
Clelia Peano ◽  
Cecilia Deantonio ◽  
Lucia Perletti ◽  
Alessandro Pietrelli ◽  
...  
Keyword(s):  
Burkholderia Pseudomallei ◽  
Vaccine Development ◽  
Single Gene ◽  
Soluble Form ◽  
Protein Antigens ◽  
Reading Frame ◽  
X Ray Crystallography ◽  
Conserved Domain ◽  
Structural Vaccinology ◽  
Selection Of

The 1.8 Å resolution crystal structure of a conserved domain of the potential Burkholderia pseudomallei antigen and trimeric autotransporter BPSL2063 is presented as a structural vaccinology target for melioidosis vaccine development. Since BPSL2063 (1090 amino acids) hosts only one conserved domain, and the expression/purification of the full-length protein proved to be problematic, a domain-filtering library was generated using β-lactamase as a reporter gene to select further BPSL2063 domains. As a result, two domains (D1 and D2) were identified and produced in soluble form in Escherichia coli. Furthermore, as a general tool, a genomic open reading frame-filtering library from the B. pseudomallei genome was also constructed to facilitate the selection of domain boundaries from the entire ORFeome. Such an approach allowed the selection of three potential protein antigens that were also produced in soluble form. The results imply the further development of ORF-filtering methods as a tool in protein-based research to improve the selection and production of soluble proteins or domains for downstream applications such as X-ray crystallography.

scholarly journals Predicting and Designing Epitope Ensemble Vaccines against HTLV-1

2020 ◽  
Vol 16 (4) ◽  
Author(s):  
Saruar Alam ◽  
Md. Kamrul Hasan ◽  
Omar Hamza Bin Manjur ◽  
Akib Mahmud Khan ◽  
Zinat Sharmin ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Vaccine Development ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Effective Vaccine ◽  
Binding Prediction ◽  
Multiple Sequence ◽  
T Lymphotropic Virus ◽  
Dynamics Simulations ◽  
Epitope Binding

AbstractThe infection mechanism and pathogenicity of Human T-lymphotropic virus 1 (HTLV-1) are ambiguously known for hundreds of years. Our knowledge about this virus is recently emerging. The purpose of the study is to design a vaccine targeting the envelope glycoprotein, GP62, an outer membrane protein of HTLV-1 that has an increased number of epitope binding sites. Data collection, clustering and multiple sequence alignment of HTLV-1 glycoprotein B, variability analysis of envelope Glycoprotein GP62 of HTLV-1, population protection coverage, HLA-epitope binding prediction, and B-cell epitope prediction were performed to predict an effective vaccine. Among all the predicted peptides, ALQTGITLV and VPSSSTPL epitopes interact with three MHC alleles. The summative population protection coverage worldwide by these epitopes as vaccine candidates was found nearly 70%. The docking analysis revealed that ALQTGITLV and VPSSSTPL epitopes interact strongly with the epitope-binding groove of HLA-A*02:03, and HLA-B*35:01, respectively, as this HLA molecule was found common with which every predicted epitope interacts. Molecular dynamics simulations of the docked complexes show they form stable complexes. So, these potential epitopes might pave the way for vaccine development against HTLV-1.

scholarly journals Sub-genomic analysis of Chikungunya virus E2 mutations in Pakistani isolates potentially modulating B-cell & T-Cell immune response

2020 ◽  
Vol 37 (1) ◽  
Author(s):  
Bilal Ahmed Khan ◽  
Saif Ullah ◽  
Amanullah Lail ◽  
Saeed Khan
Keyword(s):  
Immune Response ◽  
T Cell ◽  
B Cell ◽  
Chikungunya Virus ◽  
Vaccine Development ◽  
Epitope Prediction ◽  
Genomic Analysis ◽  
Cell Immune Response ◽  
Population Coverage ◽  
Cross Sectional

Background & Objectives: The Chikungunya virus (CHIKV) transmitted to the humans through Aedes species of the mosquitoes. In December 2016, a severe outbreak reported from Pakistan. However, there is no vaccine or anti-viral treatment currently available so host immune response against CHIKV gained significant interest. Therefore, this study was conducted to identify the mutations in CHIKV E2 region of currently circulating Pakistani strains & determine their potential immunogenicity in Pakistani population. Methods: It was a cross sectional study in which a total of 60 CHIKV PCR positive samples were collected from Molecular Department of Pathology, Dow University of Health Sciences (DUHS), Karachi during November 2017 to February 2018. CHIKV E2 gene was amplified by PCR & sequenced. Sequences were analyzed by using bioinformatic tools followed by epitope prediction in E2 sequences by In-silico immunoinformatic approach. Results: Several single nucleotide variations (SNVs) were identified in Pakistani isolates with six novel mutations in E2 sequences. Immunoinformatic analyses showed more proteasomal sites, CTL & B-Cell epitopes in Pakistani strains with respect to S27 prototype with 69.4% population coverage against these epitopes in Pakistan. The study also identified key mutations responsible for generation of unique epitopes and HLA restriction in Pakistani isolates. The strain specific mutations revealed the current outbreak was caused by ESCA.IOL lineage of CHIKV. Conclusion: The evolution of E2 protein in Pakistani strains has increased its immunogenicity in comparison to ancestral s27 strain. The identification of most immunogenic and conserved epitopes with high population coverage has high potential to be used in vaccine development against these local strains. doi: https://doi.org/10.12669/pjms.37.1.3236 How to cite this:Khan BA, Saifullah, Lail A, Khan S. Sub-genomic analysis of Chikungunya virus E2 mutations in Pakistani isolates potentially modulating B-cell & T-Cell immune response. Pak J Med Sci. 2021;37(1):93-98. doi: https://doi.org/10.12669/pjms.37.1.3236 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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