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

Nipah virus (NiV) is an emerging zoonotic virus responsible to cause several serious outbreaks in South Asian region with high mortality rate of 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 infection. Recently, some Multi-Epitope Vaccines (MEV) has been proposed but they involve limited number of epitopes which further 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 design two multi-epitope vaccines (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-γ 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 β-defensin 2 and β-defensin 3 were used as adjuvants to enhance the immune response of both the MEVs. The molecular dynamics simulation study of MEVs-TLR3(ECD) (Toll-Like Receptor 3 Ectodomain) complex indicated 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, both the design of CTL and HTL MEVs could be cloned, expressed and tried for in-vivo validations (animal trails) as potential vaccine candidates against NiV infection.

Novel ‘GaEl antigenic patches’ identified by ‘reverse epitomics’ approach to design multi-patch vaccines against NIPAH infection, a silent threat to global human health

“…These epitopes were further utilized to identify the potentially immunogenic multiple epitope cluster based CTL Ag-Patches from the entire proteome of the SRAS-CoV-2. The screened epitopes are in consensus with the previous studies 38 . Supplementary Table S3: High Percentile Ranking HTL epitopes-HLA allele pairs screened from entire proteome of SARS-CoV-2 by the "MHC-II Binding Predictions" tool of IEDB.…”

“…These epitopes were further utilized to identify the potentially immunogenic multiple epitope cluster based CTL Ag-Patches from the entire proteome of the SRAS-CoV-2. The screened epitopes are in consensus with the previous studies 38 .…”

“…The herewith suggested GaEl Ag-Patches are expected to result in up to 776 overlapping epitopes upon intercellular proteolytic chop down by Antigen Presenting Cells (APC). Such large numbers of epitopes cannot be accommodated by Multi-Epitope Vaccines (MEV) candidates 38,86–90 . Furthermore, lagging behind to MPVs in respect of encoding a high number of epitopes, the MEVs with short peptide of epitopes might also result in wrong or missfoled peptides output upon intracellular proteolytic chop down by APC.…”

“…Majority of the vaccine design against NiV are focused on the single protein like G and F proteins, protein subunits or the epitopes from NiV proteins 38,[86][87][88][89][90] . The recent strategies for the design and development of vaccines to combat NiV involve subunit vaccines or multi-epitope vaccines.…”

“…In recent studies a number of B cell and T cell epitope candidates from different NiV proteins have been reported. Additionally, a number of vaccine design approaches and vaccine candidates including multi epitope vaccines were reported [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] . However, using a single or a small number of epitopes might be limiting the vaccine potential.…”