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Discovery of T-cell Driven Subunit Vaccines from Zika Virus Genome: An Immunoinformatics Approach.

ABSTRACT: The recent outbreaks of Zika virus and the absence of a specific therapy have necessitated to identify T-cell-stimulating antigenic peptides as potential subunit vaccine candidates. The translated ssRNA (+) genome of Zika virus was explored in EMBOSS antigenic and VaxiJen to predict 63 peptides as potential antigens. Three MHC-II binding peptide prediction tools, viz. NetMHCIIpan, PREDIVAC and immune epitope database (IEDB) were employed in consensus on 63 antigenic peptides to propose 14 T-helper cell epitopes. Similarly, analysis on 63 antigenic peptides through NetMHC, NetCTL and IEDB MHC-I binding peptide prediction tool led to identification of 14 CTL epitopes. Seven T-cell epitopes, C:44-66, M:135-149, NS2A:124-144, NS3:421-453, NS3:540-554, NS4B:90-134 and NS4B:171-188, are observed to share overlapping MHC-I and MHC-II binding motifs and hence, are being proposed to constitute minimum T-cell antigens to elicit protective T-cell immune response against Zika. Three of them, C:44-66, NS3:421-453 and NS3:540-554 are identified to be conserved across all the selected strains of Zika virus. Moreover, the 21 T-cell epitopes are non-self to humans and exhibited good coverage in variable populations of 14 geographical locations. Therefore, 21 T-cell epitopes are proposed as potential subunit vaccines against Zika virus.

SUBMITTER: Pradhan D

PROVIDER: S-EPMC7091030 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Discovery of T-cell Driven Subunit Vaccines from Zika Virus Genome: An Immunoinformatics Approach.

Pradhan Dibyabhaba D Yadav Monika M Verma Rashi R Khan Noor Saba NS Jena Lingaraja L Jain Arun Kumar AK

Interdisciplinary sciences, computational life sciences 20171101 4

The recent outbreaks of Zika virus and the absence of a specific therapy have necessitated to identify T-cell-stimulating antigenic peptides as potential subunit vaccine candidates. The translated ssRNA (+) genome of Zika virus was explored in EMBOSS antigenic and VaxiJen to predict 63 peptides as potential antigens. Three MHC-II binding peptide prediction tools, viz. NetMHCIIpan, PREDIVAC and immune epitope database (IEDB) were employed in consensus on 63 antigenic peptides to propose 14 T-help ...[more]

PMID: 29094318

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Project description:Epstein-Barr virus (EBV) is a lymphotropic virus responsible for numerous epithelial and lymphoid cell malignancies, including gastric carcinoma, Hodgkin's lymphoma, nasopharyngeal carcinoma, and Burkitt lymphoma. Hundreds of thousands of people worldwide get infected with this virus, and in most cases, this viral infection leads to cancer. Although researchers are trying to develop potential vaccines and drug therapeutics, there is still no effective vaccine to combat this virus. In this study, the immunoinformatics approach was utilized to develop a potential multiepitope subunit vaccine against the two most common subtypes of EBV, targeting three of their virulent envelope glycoproteins. Eleven cytotoxic T lymphocyte (CTL) epitopes, 11 helper T lymphocyte (HTL) epitopes, and 10 B-cell lymphocyte (BCL) epitopes were predicted to be antigenic, nonallergenic, nontoxic, and fully conserved among the two subtypes, and nonhuman homologs were used for constructing the vaccine after much analysis. Later, further validation experiments, including molecular docking with different immune receptors (e.g., Toll-like receptors [TLRs]), molecular dynamics simulation analyses (including root means square deviation [RMSD], root mean square fluctuation [RMSF], radius of gyration [Rg], principal-component analysis [PCA], dynamic cross-correlation [DCC], definition of the secondary structure of proteins [DSSP], and Molecular Mechanics Poisson-Boltzmann Surface Area [MM-PBSA]), and immune simulation analyses generated promising results, ensuring the safe and stable response of the vaccine with specific immune receptors after potential administration within the human body. The vaccine's high binding affinity with TLRs was revealed in the docking study, and a very stable interaction throughout the simulation proved the potential high efficacy of the proposed vaccine. Further, in silico cloning was also conducted to design an efficient mass production strategy for future bulk industrial vaccine production. IMPORTANCE Epstein-Barr virus (EBV) vaccines have been developing for over 30 years, but polyphyletic and therapeutic vaccines have failed to get licensed. Our vaccine surpasses the limitations of many such vaccines and remains very promising, which is crucial because the infection rate is higher than most viral infections, affecting a whopping 90% of the adult population. One of the major identifications covers a holistic analysis of populations worldwide, giving us crucial information about its effectiveness for everyone's unique immunological system. We targeted three glycoproteins that enhance the virulence of the virus to design an epitope-based polyvalent vaccine against two different strains of EBV, type 1 and 2. Our methodology in this study is nonconventional yet swift to show effective results while designing vaccines.

Project description:IntroductionThe Zika virus is an emerging Flavivirus known to cause Zika infection in humans. It is associated with severe health problems such as microcephaly and Guillain-Barré syndrome post the Brazilian epidemic in 2015-16. The spread of the Zika virus to the Asian subcontinent, especially to India is a matter of great concern. Two recent co-circulating Indian Zika virus strains such as Rajasthan and Maharashtra detected in 2018 and 2021 were studied to identify B-cell epitopes in the envelope and non-structural 1 protein as these epitopes are major indicators of robust humoral immune response. The study aimed at identifying novel epitopes, followed by molecular docking with potent Zika virus-specific monoclonal antibodies. The novel epitopes identified in this study shall be essential in designing multi-epitope vaccines capable of inducing antibody response against Zika virus infection.MethodsABCpred, BepiPred 2.0 and Kolaskar-Tongaonkar methods were used for predicting the linear B-cell epitopes, and Discotope 2.0 and ElliPro were used for the prediction of conformational epitopes. Linear epitopes were further checked for protective antigenicity, allergenicity and toxicity. Based on the stringent study design criteria, only the novel epitopes were considered for molecular docking with complementary determining regions of potent Zika virus-specific monoclonal antibodies.ResultsNineteen linear and five conformational epitopes were shortlisted based on protective potential, non-allergic and non-toxic properties for Zika virus E protein, from which nine linear and three conformational epitopes were identified as novel. Molecular docking studies revealed that the novel linear epitopes, one each from EDIII, EDII, EDI and EDI/DIII hinge were involved in epitope-CDR interactions with potent neutralizing Zika virus E-specific mouse monoclonal antibody ZV-67. Moreover, the novel EDII epitope was exclusively engaged in epitope-CDR interactions of potent neutralizing Zika virus E-specific human monoclonal antibody Z3L1. None of the linear epitopes of Zika virus NS1 were ascertained as novel based on our study criteria. Conformational epitopes were identified as novel for NS1 protein.ConclusionThis study identified Zika virus-specific novel epitopes of envelope and non-structural -1 proteins in the currently co-circulating Indian strains. Furthermore, in-silico validation through molecular docking added insight into antigen-antibody interactions, paving way for future in vitro and in vivo studies.

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Discovery of T-cell Driven Subunit Vaccines from Zika Virus Genome: An Immunoinformatics Approach.

Publications

Discovery of T-cell Driven Subunit Vaccines from Zika Virus Genome: An Immunoinformatics Approach.

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