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.
Highlights
Influenza A viruses (IAVs) cause a highly contagious respiratory disease in swine, a problem that has a significant impact on food production.[1]
As T-cell epitopes that are similar in vaccine and challenge strains may be responsible for protection in the absence of cross-reactive antibodies, we developed a method for T-cell epitope content comparison (EpiCC) that assesses the relatedness of class I and II epitopes across antigens and predicts potential vaccine efficacy based on a relatedness threshold
We evaluated whether T- cell epitope relatedness could explain protection of pigs that were vaccinated with a commercial inactivated vaccine and challenged with heterologous H1N1 IAV when cross-reactive antibodies were absent
Summary
Predicting vaccine efficacy against emerging pathogen strains is a significant problem in human and animal vaccine design. 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. Objective: We 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. Methods: T-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®). Results: Higher EpiCC scores were associated with greater protection by the vaccine against strains for 23 field IAV strain vaccine comparisons. KEYWORDS computational immunology, hemagglutinin, influenza A viruses, swine influenza H1 viruses, swine leukocyte antigen, T-cell epitope content comparison, T-cell epitope prediction, vaccine efficacy
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