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

Background Predicting 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...

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Published in:	Influenza and other respiratory viruses 2017-11, Vol.11 (6), p.531-542
Main Authors:	Gutiérrez, Andres H., Rapp‐Gabrielson, Vicki J., Terry, Frances E., Loving, Crystal L., Moise, Leonard, Martin, William D., De Groot, Anne S.
Format:	Article
Language:	eng
Subjects:	Algorithms Analysis Animal vaccines Animals Antibodies Antigenic determinants computational immunology Computer applications Computers, Molecular Cross Protection - genetics Cross Protection - immunology Cross-reactivity Development and progression Effectiveness Epitope Mapping - methods Epitopes Epitopes, T-Lymphocyte - chemistry Epitopes, T-Lymphocyte - genetics Epitopes, T-Lymphocyte - immunology Hemagglutination Hemagglutination inhibition hemagglutinin Hemagglutinins Hemagglutinins - chemistry Hemagglutinins - genetics Hemagglutinins - immunology Histocompatibility Antigens Class I - immunology Immunology Influenza Influenza A Influenza A virus - chemistry Influenza A virus - immunology influenza A viruses Influenza vaccines Lectins Livestock Lymphocytes T Medical research Medicine, Experimental Original Orthomyxoviridae Infections - virology Phylogeny Sequence Analysis, Protein - methods Strains (organisms) Swine Swine Diseases - virology swine influenza H1 viruses swine leukocyte antigen T cells T‐cell epitope content comparison T‐cell epitope prediction Vaccine development Vaccine efficacy Vaccine Potency Vaccines Viruses Wildlife conservation
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Summary:	Background Predicting 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. 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®). Scores were compared to experimental data from previous efficacy studies. Results Higher 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. Conclusion EpiCC 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.
ISSN:	1750-2640 1750-2659