Designing a novel and combinatorial multi-antigenic epitope-based vaccine "MarVax" against Marburg virus-a reverse vaccinology and immunoinformatics approach.

Abstract

Context: Marburg virus (MARV) is a member of the Filoviridae family and causes Marburg virus disease (MVD) among humans and primates. With fatality rates going up to 88%, there is currently no commercialized cure or vaccine to combat the infection. The National Institute of Allergy and Infectious Diseases (NIAID) classified MARV as priority pathogen A, which presages the need for a vaccine candidate which can provide stable, long-term adaptive immunity. The surface glycoprotein (GP) and fusion protein (FP) mediate the adherence, fusion, and entry of the virus into the host cell via the TIM-I receptor. Being important antigenic determinants, studies reveal that GP and FP are prone to evolutionary mutations, underscoring the requirement of a vaccine construct capable of eliciting a robust and sustained immune response. In this computational study, a reverse vaccinology approach was employed to design a combinatorial vaccine from conserved and antigenic epitopes of essential viral proteins of MARV, namely GP, VP24, VP30, VP35, and VP40 along with an endogenous protein large polymerase (L).

Methods: Epitopes for T-cell and B-cell were predicted using TepiTool and ElliPro, respectively. The surface-exposed TLRs like TLR2, TLR4, and TLR5 were used to screen high-binding affinity epitopes using the protein-peptide docking platform MdockPeP. The best binding epitopes were selected and assembled with linkers to design a recombinant multi-epitope vaccine construct which was then modeled in Robetta. The in silico biophysical and biochemical analyses of the recombinant vaccine were performed. The docking and MD simulation of the vaccine using WebGro and CABS-Flex against TLRs support the stable binding of vaccine candidates. A virtual immune simulation to check the immediate and long-term immunogenicity was carried out using the C-ImmSim server.

Results: The biochemical characteristics and docking studies with MD simulation establish the recombinant protein vaccine construct MarVax as a stable, antigenic, and potent vaccine molecule. Immune simulation studies reveal 1-year passive immunity which needs to be validated by in vivo studies.