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In silico-based vaccine design against Ebola virus glycoprotein.

ABSTRACT: Ebola virus (EBOV) is one of the lethal viruses, causing more than 24 epidemic outbreaks to date. Despite having available molecular knowledge of this virus, no definite vaccine or other remedial agents have been developed yet for the management and avoidance of EBOV infections in humans. Disclosing this, the present study described an epitope-based peptide vaccine against EBOV, using a combination of B-cell and T-cell epitope predictions, followed by molecular docking and molecular dynamics simulation approach. Here, protein sequences of all glycoproteins of EBOV were collected and examined via in silico methods to determine the most immunogenic protein. From the identified antigenic protein, the peptide region ranging from 186 to 220 and the sequence HKEGAFFLY from the positions of 154-162 were considered the most potential B-cell and T-cell epitopes, correspondingly. Moreover, this peptide (HKEGAFFLY) interacted with HLA-A*32:15 with the highest binding energy and stability, and also a good conservancy of 83.85% with maximum population coverage. The results imply that the designed epitopes could manifest vigorous enduring defensive immunity against EBOV.

SUBMITTER: Dash R

PROVIDER: S-EPMC5367765 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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In silico-based vaccine design against Ebola virus glycoprotein.

Dash Raju R Das Rasel R Junaid Md M Akash Md Forhad Chowdhury MF Islam Ashekul A Hosen Sm Zahid SZ

Advances and applications in bioinformatics and chemistry : AABC 20170321

Ebola virus (EBOV) is one of the lethal viruses, causing more than 24 epidemic outbreaks to date. Despite having available molecular knowledge of this virus, no definite vaccine or other remedial agents have been developed yet for the management and avoidance of EBOV infections in humans. Disclosing this, the present study described an epitope-based peptide vaccine against EBOV, using a combination of B-cell and T-cell epitope predictions, followed by molecular docking and molecular dynamics sim ...[more]

PMID: 28356762

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Project description:The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. No vaccine or antiviral is currently FDA approved. To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSV?G) and bear EBOV glycoprotein (GP). These pseudovirions mediate a single round of infection. Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. The prime/boost regimen provided significantly better protection than a single dose. As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSV?G bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. Using a prime/boost strategy, high doses of GP/VSV?G partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSV?G and did not provide cross protection against Sudan virus. As reported for other EBOV vaccine platforms, the protection conferred correlated with the quantity of EBOV GP-specific Ig produced but not with the production of neutralizing antibodies. Our results show that EBOV GP/VSV?G pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. VSV?G pseudovirion vaccines may prove as efficacious and have better safety, but they have not been tested to date. Thus, we tested the efficacy of VSV?G pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. We found that wild-type Ebola virus glycoprotein, in the context of this platform, provides robust protection of EBOV-challenged mice. Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy.

Project description:BackgroundInfluenza A virus is one of the leading causes of annual mortality. The emerging of novel escape variants of the influenza A virus is still a considerable challenge in the annual process of vaccine production. The evolution of vaccines ranks among the most critical successes in medicine and has eradicated numerous infectious diseases. Recently, multi-epitope vaccines, which are based on the selection of epitopes, have been increasingly investigated.ResultsThis study utilized an immunoinformatic approach to design a recombinant multi-epitope vaccine based on a highly conserved epitope of hemagglutinin, neuraminidase, and membrane matrix proteins with fewer changes or mutate over time. The potential B cells, cytotoxic T lymphocytes (CTL), and CD4 T cell epitopes were identified. The recombinant multi-epitope vaccine was designed using specific linkers and a proper adjuvant. Moreover, some bioinformatics online servers and datasets were used to evaluate the immunogenicity and chemical properties of selected epitopes. In addition, Universal Immune System Simulator (UISS) in silico trial computational framework was run after influenza exposure and recombinant multi-epitope vaccine administration, showing a good immune response in terms of immunoglobulins of class G (IgG), T Helper 1 cells (TH1), epithelial cells (EP) and interferon gamma (IFN-g) levels. Furthermore, after a reverse translation (i.e., convertion of amino acid sequence to nucleotide one) and codon optimization phase, the optimized sequence was placed between the two EcoRV/MscI restriction sites in the PET32a+ vector.ConclusionsThe proposed "Recombinant multi-epitope vaccine" was predicted with unique and acceptable immunological properties. This recombinant multi-epitope vaccine can be successfully expressed in the prokaryotic system and accepted for immunogenicity studies against the influenza virus at the in silico level. The multi-epitope vaccine was then tested with the Universal Immune System Simulator (UISS) in silico trial platform. It revealed slight immune protection against the influenza virus, shedding the light that a multistep bioinformatics approach including molecular and cellular level is mandatory to avoid inappropriate vaccine efficacy predictions.

Project description:The Ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. Currently, replication defective adenovirus-based Ebola vaccine is being studied in a phase I clinical trial. Another Ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to Ebola infection. In this report, we modified the common recombinant adenovirus serotype 5-based Ebola vaccine expressing the wild-type ZEBOV glycoprotein sequence from a CMV promoter (Ad-CMVZGP). The immune response elicited by this improved expression cassette vector (Ad-CAGoptZGP) and its ability to afford protection against lethal ZEBOV challenge in mice was compared to the standard Ad-CMVZGP vector.Ad-CMVZGP was previously shown to protect mice, guinea pigs and nonhuman primates from an otherwise lethal challenge of Zaire ebolavirus. The antigenic expression cassette of this vector was improved through codon optimization, inclusion of a consensus Kozak sequence and reconfiguration of a CAG promoter (Ad-CAGoptZGP). Expression of GP from Ad-CAGoptZGP was substantially higher than from Ad-CMVZGP. Ad-CAGoptZGP significantly improved T and B cell responses at doses 10 to 100-fold lower than that needed with Ad-CMVZGP. Additionally, Ad-CAGoptZGP afforded full protections in mice against lethal challenge at a dose 100 times lower than the dose required for Ad-CMVZGP. Finally, Ad-CAGoptZGP induced full protection to mice when given 30 minutes post-challenge.We describe an improved adenovirus-based Ebola vaccine capable of affording post-exposure protection against lethal challenge in mice. The molecular modifications of the new improved vaccine also translated in the induction of significantly enhanced immune responses and complete protection at a dose 100 times lower than with the previous generation adenovirus-based Ebola vaccine. Understanding and improving the molecular components of adenovirus-based vaccines can produce potent, optimized product, useful for vaccination and post-exposure therapy.

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In silico-based vaccine design against Ebola virus glycoprotein.

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In silico-based vaccine design against Ebola virus glycoprotein.

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