Exploring the structural basis to develop efficient multi-epitope vaccines displaying interaction with HLA and TAP and TLR3 molecules to prevent NIPAH infection, a global threat to human health

Abstract

BackgroundNipah virus (NiV) is an emerging zoonotic virus that caused several serious outbreaks in the South Asian region with high mortality rates ranging from 40 to 90% since 2001. NiV infection causes lethal encephalitis and respiratory disease with the symptom of endothelial cell-cell fusion. No specific vaccine has yet been reported against NiV. Methodology and Principal FindingsRecently, the design of some Multi-Epitope Vaccines (MEV) has been proposed but that involves vary limited number of epitopes which limits the potential of vaccine. To address the urgent need for a specific and effective vaccine against NiV infection, in the present study, we have designed two MEVs composed of 33 Cytotoxic T lymphocyte (CTL) epitopes and 38 Helper T lymphocyte (HTL) epitopes. Both the MEVs carry potential B cell linear epitope overlapping regions, B cell discontinuous epitopes as well as IFN-{gamma} inducing epitopes. Hence the designed MEVs carry potential to elicit cell-mediated as well as humoral immune response. Selected CTL and HTL epitopes were validated for their stable molecular interactions with HLA class I and II alleles as well as in case of CTL epitopes, with human transporter associated with antigen processing (TAP). Human {beta}-defensin 2 and {beta}-defensin 3 were used as adjuvants to enhance the immune response of both the MEVs. Molecular dynamics simulation studies of MEVs-TLR3 ectodomain (Toll-Like Receptor 3) complex indicate the stable molecular interaction. Further, the codon optimized cDNA of both the MEVs has shown high expression potential in the mammalian host cell line (Human). Hence for further studies, the designed MEV constructs could be expressed and tried in-vivo as potential vaccine candidates against NiV. ConclusionWe conclude that the MEVs designed and in silico validated here could be highly potential vaccine candidate to combat NiV, with greater effectiveness, high specificity and large human population coverage worldwide. AUTHOR SUMMARYNipah Virus (NiV) has caused several outbreaks in past two decades calming large number of human lives. Our present work aims to design and in silico validate Multi-Epitope Vaccine against NiV. The current approach to design vaccine involves whole virus or full length proteins as vaccine candidates against NiV. These approaches carry chances of raising the unwanted non-neutralizing antibodies which have been found to cause clinical complexities. Recently few Multi-Epitope vaccines have also been proposed, but they have involved limited number of epitopes for vaccine design in result limiting the effectiveness and human population coverage. Here in our MEVs we have involved all the proteins of NiV to design the vaccine. Moreover since we have used in silico validated epitopes we may conclude that the here proposed MEVs would be highly specific, effective and potential vaccine candidate to combat NiV with large human population coverage worldwide.