T‐cell epitope content comparison (EpiCC) of swine H1 influenza A virus hemagglutinin

Abstract

BackgroundPredicting vaccine efficacy against emerging pathogen strains is a significant problem in human and animal vaccine design. T‐cell epitope cross‐conservation may play an important role in cross‐strain vaccine efficacy. While influenza A virus (IAV) hemagglutination inhibition (HI) antibody titers are widely used to predict protective efficacy of 1 IAV vaccine against new strains, no similar correlate of protection has been identified for T‐cell epitopes.ObjectiveWe developed a computational method (EpiCC) that facilitates pairwise comparison of protein sequences based on an immunological property—T‐cell epitope content—rather than sequence identity, and evaluated its ability to classify swine IAV strain relatedness to estimate cross‐protective potential of a vaccine strain for circulating viruses.MethodsT‐cell epitope relatedness scores were assessed for 23 IAV HA sequences representing the major H1 swine IAV phylo‐clusters circulating in North American swine and HA sequences in a commercial inactivated vaccine (FluSure XP ®). Scores were compared to experimental data from previous efficacy studies.ResultsHigher EpiCC scores were associated with greater protection by the vaccine against strains for 23 field IAV strain vaccine comparisons. A threshold for EpiCC relatedness associated with full or partial protection in the absence of cross‐reactive HI antibodies was identified. EpiCC scores for field strains for which FluSure protective efficacy is not yet available were also calculated.ConclusionEpiCC thresholds can be evaluated for predictive accuracy of protection in future efficacy studies. EpiCC may also complement HI cross‐reactivity and phylogeny for selection of influenza strains in vaccine development.

Quantifying the Persistence of Vaccine-Related T Cell Epitopes in Circulating Swine Influenza A Strains from 2013–2017

“…Higher EpiCC scores are thought to be associated with greater protection by vaccines against challenge strains [ 23 ]. For MEpiV vaccine class I epitopes, the highest EpiCC score is found for H1N1 swine IAVs (EpiCC score of 0.0256 with 98.5% conservation when normalized to the MEpiV baseline), and the lowest for H3N2 (EpiCC score of 0.0100 with 38.5% conservation when normalized to the MEpiV baseline).…”

“…In order to determine the conservation of the T cell epitopes in the MEpiV among the three-circulating swine IAV subtypes, we applied EpiCC to facilitate the pairwise comparison of protein sequences [ 23 ]. This method of comparison is based on an immunological property expressed in terms of T cell epitope content which incorporated JMX computation, rather than sequence identity.…”

Better Epitope Discovery, Precision Immune Engineering, and Accelerated Vaccine Design Using Immunoinformatics Tools

“…The EpiCC tool has been applied successfully to describe vaccine protection against challenge strains for influenza A (58) and is being used prospectively to develop combination vaccines for additional pathogens affecting swine. The EpiCC tool is the most recent tool to be integrated into iVAX; potential applications include determining where influenza virus "spillover" events will occur (transmission of influenza from swine to humans) and "predicting the next pandemic" in collaboration with influenza researchers at the University of Georgia, Athens, USA.…”

Virus-Induced T Cell-Mediated Heterologous Immunity and Vaccine Development

“…It has been demonstrated that epitope-rich regions within the nucleoprotein (NP) of the influenza virus contain highly conserved epitopes and therefore present promising targets for a T cell-mediated vaccine due to cross-reactivity with distinct strains (21). Gutiérrez et al developed a computational method to compare the efficacy of conserved T cell epitopes (EpiCC), which may complement current methods for selecting the best composition of an associated vaccine (22). Furthermore, CD8 + T cells recognizing different NP variants were associated with cross-reactive TCR clonotypes against distinct strains (23).…”