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Epitope mapping of Ebola virus dominant and subdominant glycoprotein epitopes facilitates construction of an epitope-based DNA vaccine able to focus the antibody response in mice.

ABSTRACT: We performed epitope mapping studies on the major surface glycoprotein (GP) of Ebola virus (EBOV) using Chemically Linked Peptides on Scaffolds (CLIPS), which form linear and potential conformational epitopes. This method identified monoclonal antibody epitopes and predicted additional epitopes recognized by antibodies in polyclonal sera from animals experimentally vaccinated against or infected with EBOV. Using the information obtained along with structural modeling to predict epitope accessibility, we then constructed 2 DNA vaccines encoding immunodominant and subdominant epitopes predicted to be accessible on EBOV GP. Although a construct designed to produce a membrane-bound oligopeptide was poorly immunogenic, a construct generating a secreted oligopeptide elicited strong antibody responses in mice. When this construct was administered as a boost to a DNA vaccine expressing the complete EBOV GP gene, the resultant antibody response was focused largely toward the less immunodominant epitopes in the oligopeptide. Taken together, the results of this work suggest a utility for this method for immune focusing of antibody responses elicited by vaccination.

SUBMITTER: Mitchell DAJ

PROVIDER: S-EPMC5718802 | biostudies-other | 2017 Dec

REPOSITORIES: biostudies-other

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Epitope mapping of Ebola virus dominant and subdominant glycoprotein epitopes facilitates construction of an epitope-based DNA vaccine able to focus the antibody response in mice.

Mitchell Daniel A J DAJ Dupuy Lesley C LC Sanchez-Lockhart Mariano M Palacios Gustavo G Back Jaap W JW Shimanovskaya Katya K Chaudhury Sidhartha S Ripoll Daniel R DR Wallqvist Anders A Schmaljohn Connie S CS

Human vaccines & immunotherapeutics 20170712 12

We performed epitope mapping studies on the major surface glycoprotein (GP) of Ebola virus (EBOV) using Chemically Linked Peptides on Scaffolds (CLIPS), which form linear and potential conformational epitopes. This method identified monoclonal antibody epitopes and predicted additional epitopes recognized by antibodies in polyclonal sera from animals experimentally vaccinated against or infected with EBOV. Using the information obtained along with structural modeling to predict epitope accessibi ...[more]

PMID: 28699812

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Project description:The discovery of a new SARS-CoV-2 virus strain in South Africa presents a major public health threat, therefore contributing to increased infections and transmission rates during the second wave of the global pandemic. This study lays the groundwork for the development of a novel subunit vaccine candidate from the circulating strains of South African SARS-CoV-2 and provides an understanding of the molecular epidemiological trend of the circulating strains. A total of 475 whole-genome nucleotide sequences from South Africa submitted between December 1, 2020 and February 15, 2021 available at the GISAID database were retrieved based on its size, coverage level and hosts. To obtain the distribution of the clades and lineages of South African SARS-CoV-2 circulating strains, the metadata of the sequence retrieved were subjected to an epidemiological analysis. There was a prediction of the cytotoxic T lymphocytes (CTL), Helper T cells (HTL) and B-cell epitopes. Furthermore, there was allergenicity, antigenicity and toxicity predictions on the epitopes. The analysis of the physicochemical properties of the vaccine construct was performed; the secondary structure, tertiary structure and B-cell 3D conformational structure of the vaccine construct were predicted. Also, molecular binding simulations and dynamics simulations were adopted in the prediction of the vaccine construct's stability and binding affinity with TLRs. Result obtained from the metadata analysis indicated lineage B.1.351 to be in higher circulation among various circulating strains of SARS-CoV-2 in South Africa and GH has the highest number of circulating clades. The construct of the novel vaccine was antigenic, non-allergenic and non-toxic. The Instability index (II) score and aliphatic index were estimated as 41.74 and 78.72 respectively. The computed half-life in mammalian reticulocytes was 4.4 h in vitro, for yeast and in E. coli was >20 h and >10 h in vivo respectively. The grand average of hydropathicity (GRAVY) score is estimated to be -0.129, signifying the hydrophilic nature of the protein. The molecular docking indicates that the vaccine construct has a high binding affinity towards the TLRs with TLR 3 having the highest binding energy (-1203.2 kcal/mol) and TLR 9 with the lowest (-1559.5 kcal/mol). These results show that the vaccine construct is promising and should be evaluated using animal model.

Dataset Information

Epitope mapping of Ebola virus dominant and subdominant glycoprotein epitopes facilitates construction of an epitope-based DNA vaccine able to focus the antibody response in mice.

Publications

Epitope mapping of Ebola virus dominant and subdominant glycoprotein epitopes facilitates construction of an epitope-based DNA vaccine able to focus the antibody response in mice.

Similar Datasets

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