Nipah virus (NiV) is a zoonotic virus that causes lethal
encephalitis
and respiratory disease with the symptom of endothelial cell–cell
fusion. Several NiV outbreaks have been reported since 1999 with nearly
annual occurrences in Bangladesh. The outbreaks had high mortality
rates ranging from 40 to 90%. No specific vaccine has yet been reported
against NiV. Recently, several vaccine candidates and different designs
of vaccines composed of epitopes against NiV were proposed. Most of
the vaccines target single protein or protein complex subunits of
the pathogen. The multiepitope vaccines proposed also cover a largely
limited number of epitopes, and hence, their efficiency is still uncertain.
To address the urgent need for a specific and effective vaccine against
NiV infection, in the present study, we have utilized the “reverse
epitomics” approach (“overlapping-epitope-clusters-to-patches”
method) to identify “antigenic patches” (Ag-Patches)
and utilize them as immunogenic composition for multipatch vaccine
(MPV) design. The designed MPVs were analyzed for immunologically
crucial parameters, physiochemical properties, and interaction with
Toll-like receptor 3 ectodomain. In total, 30 CTL (cytotoxic T lymphocyte)
and 27 HTL (helper T lymphocyte) antigenic patches were identified
from the entire NiV proteome based on the clusters of overlapping
epitopes. These identified Ag-Patches cover a total of discrete 362
CTL and 414 HTL epitopes from the entire proteome of NiV. The antigenic
patches were utilized as immunogenic composition for the design of
two CTL and two HTL multipatch vaccines. The 57 antigenic patches
utilized here cover 776 overlapping epitopes targeting 52 different
HLA class I and II alleles, providing a global ethnically distributed
human population coverage of 99.71%. Such large number of epitope
coverage resulting in large human population coverage cannot be reached
with single-protein/subunit or multiepitope based vaccines. The reported
antigenic patches also provide potential immunogenic composition for
early detection diagnostic kits for NiV infection. Further, all the
MPVs and Toll-like receptor ectodomain complexes show a stable nature
of molecular interaction with numerous hydrogen bonds, salt bridges,
and nonbounded contact formation and acceptable root mean square deviation
and fluctuation. The cDNA analysis shows a favorable large-scale expression
of the MPV constructs in a human cell line. By utilizing the novel
“reverse epitomics” approach, highly immunogenic novel
“GaEl antigenic patches” (GaEl Ag-Patches), a synonym
term for “antigenic patches”, were identified and utilized
as immunogenic composition to design four MPVs against NiV. We conclude
that the novel multipatch vaccines are potential candidates to combat
NiV, with greater effectiveness, high specificity, and large human
population coverage worldwide.