23
DOI: https://doi.org/10.1186/s43141-023-00575-w
English
eng
Debroy, Bishal
Contributor
<div id="abs0005" style="margin: 0px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="sect0010" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Context</h3><div class="u-margin-s-bottom" id="sp0050" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;"><span style="margin: 0px; padding: 0px;"><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/marburgvirus" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">Marburg virus</a> (MARV) is a member of the </span><a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/filoviridae" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">Filoviridae</a><span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;"> family and causes <a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/marburgvirus" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">Marburg virus</a> disease (MVD) among humans and primates. With </span><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/mortality-rate" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">fatality rates</a><span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;"> 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 <a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/adaptive-immune-system" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">adaptive immunity</a>. The </span><a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/surface-property" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">surface</a> </span><a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/glycoprotein" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">glycoprotein</a><span style="margin: 0px; padding: 0px;"> (GP) and <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/fusion-protein" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">fusion protein</a> (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 </span></span><a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/reverse-vaccinology" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">reverse vaccinology</a> approach was employed to design a combinatorial vaccine from conserved and antigenic epitopes of essential </span></span><a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/viral-protein" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">viral proteins</a><span style="margin: 0px; padding: 0px;"> of MARV, namely GP, VP24, VP30, VP35, and VP40 along with an endogenous protein large <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/polymerase" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">polymerase</a> (L).</span></span></div></div><div id="abs0010" style="margin: 0px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="sect0015" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Methods</h3><div class="u-margin-s-bottom" id="sp0055" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;"><span style="margin: 0px; padding: 0px;">Epitopes for T-cell and B-cell were predicted using TepiTool and ElliPro, respectively. The surface-exposed <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/toll-like-receptor" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">TLRs</a><span style="margin: 0px; padding: 0px;"> like <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/tlr2" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">TLR2</a><span style="margin: 0px; padding: 0px;">, <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/tlr4" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">TLR4</a>, and </span></span></span><a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/tlr5" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">TLR5</a><span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;"> 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 <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/biochemical-analysis" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">biochemical analyses</a> of the </span><a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/recombinant-vaccine" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">recombinant vaccine</a><span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;"> were performed. The docking and <a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/dynamics" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">MD</a> simulation of the vaccine using WebGro and CABS-Flex against </span><a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/toll-like-receptor" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">TLRs</a> support the stable binding of vaccine candidates. A virtual immune simulation to check the immediate and long-term </span><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/immunogenicity" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">immunogenicity</a> was carried out using the C-ImmSim server.</span></span></div></div><div id="abs0015" style="margin: 0px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="sect0020" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Results</h3><div class="u-margin-s-bottom" id="sp0060" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;"><span style="margin: 0px; padding: 0px;">The biochemical characteristics and docking studies with MD simulation establish the <a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/recombinant-protein" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">recombinant protein</a><span style="margin: 0px; padding: 0px;"> vaccine construct MarVax as a stable, antigenic, and potent vaccine molecule. Immune simulation studies reveal 1-year <a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/passive-immunity" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">passive immunity</a> which needs to be validated by </span></span><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/in-vivo-study" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">in vivo studies</a>.</div></div>
Elsevier
December 2023
pdf
Journal of Genetic Engineering and Biotechnology
Designing a novel and combinatorial multi-antigenic epitope-based vaccine “MarVax” against Marburg virus—a reverse vaccinology and immunoinformatics approach
mixed material
Elsevier