West Nile Virus Vaccine Design by T Cell Epitope Selection: In Silico Analysis of Conservation, Functional Cross-Reactivity with the Human Genome, and Population Coverage.

Frances M Waller,Darren R Flower,Pedro A Reche

doi:10.1155/2020/7235742

Frances M Waller, Darren R Flower + Show 1 more

Open Access

https://doi.org/10.1155/2020/7235742

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Abstract

West Nile Virus (WNV) causes a debilitating and life-threatening neurological disease in humans. Since its emergence in Africa 50 years ago, new strains of WNV and an expanding geographical distribution have increased public health concerns. There are no licensed therapeutics against WNV, limiting effective infection control. Vaccines represent the most efficacious and efficient medical intervention known. Epitope-based vaccines against WNV remain significantly underexploited. Here, we use a selection protocol to identify a set of conserved prevalidated immunogenic T cell epitopes comprising a putative WNV vaccine. Experimentally validated immunogenic WNV epitopes and WNV sequences were retrieved from the IEDB and West Nile Virus Variation Database. Clustering and multiple sequence alignment identified a smaller subset of representative sequences. Protein variability analysis identified evolutionarily conserved sequences, which were used to select a diverse set of immunogenic candidate T cell epitopes. Cross-reactivity and human leukocyte antigen-binding affinities were assessed to eliminate unsuitable epitope candidates. Population protection coverage (PPC) quantified individual epitopes and epitope combinations against the world population. 3 CD8+ T cell epitopes (ITYTDVLRY, TLARGFPFV, and SYHDRRWCF) and 1 CD4+ epitope (VTVNPFVSVATANAKVLI) were selected as a putative WNV vaccine, with an estimated PPC of 97.14%.

Highlights

West Nile Virus (WNV) is a mosquito-borne Flavivirus that causes West Nile Fever (WNF) and West Nile neuroinvasive disease (WNND) in birds, humans, and horses [1]
Searching Immune Database and Analysis Resource (IEDB) identified 165 linear CD4+ and CD8+ T cell epitopes presented to T cells during WNV infection: 53 HLA class I and 112 HLA class II epitopes
Genomic sequences representing all strain variants of WNV were retrieved from the National Centre for Biotechnology Information (NCBI) West Nile Virus Variation Database. 126 unique protein sequences were retrieved

Summary

Introduction

West Nile Virus (WNV) is a mosquito-borne Flavivirus that causes West Nile Fever (WNF) and West Nile neuroinvasive disease (WNND) in birds, humans, and horses [1]. Originating in the West Nile regions of Uganda in 1937, WNV has become a prevalent human infection. Before mid-1990, the virus was confined to Africa and Europe, spread to North America, the Middle East, and West Asia. WNV infection manifests as one of three disease states: asymptomatic carrier, West Nile Fever (WNF), and West Nile neuroinvasive disease (WNND) [1]. Asymptomatic carriers represent 75% of all cases, with 25% presenting with WNF or WNND [2]. WNF is a mild, self-limiting disease which presents as general fever, malaise, and muscle and gastrointestinal pain [3]. Overall mortality is ~4.2% but rises to 9.6% in WNND

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