Abstract

When swine flu vaccines and circulating influenza A virus (IAV) strains are poorly matched, vaccine-induced antibodies may not protect from infection. Highly conserved T cell epitopes may, however, have a disease-mitigating effect. The degree of T cell epitope conservation among circulating strains and vaccine strains can vary, which may also explain differences in vaccine efficacy. Here, we evaluate a previously developed conserved T cell epitope-based vaccine and determine the persistence of T cell epitope conservation over time. We used a pair-wise homology score to define the conservation between the vaccine’s swine leukocyte antigen (SLA) class I and II-restricted epitopes and T cell epitopes found in 1272 swine IAV strains sequenced between 2013 and 2017. Twenty-four of the 48 total T cell epitopes included in the epitope-based vaccine were highly conserved and found in >1000 circulating swine IAV strains over the 5-year period. In contrast, commercial swine IAV vaccines developed in 2013 exhibited a declining conservation with the circulating IAV strains over the same 5-year period. Conserved T cell epitope vaccines may be a useful adjunct for commercial swine flu vaccines and to improve protection against influenza when antibodies are not cross-reactive.

Highlights

  • When a new strain of pathogen emerges, the first question asked is often whether existing vaccines might be effective against it

  • HA sequences of inactivated swine influenza A virus (IAV) vaccine comprised of one H1N1, one H1N2, and two H3N2 strains were provided by Zoetis to facilitate the comparison of T cell epitope conservation in the epitope-based and inactivated virus vaccine, applying the same immunoinformatic analysis pipeline

  • The goal of this study was to determine whether a vaccine designed in 2013 may continue to provide cell-mediated immunity (CMI) boosting as was illustrated in 2019 [11]

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Summary

Introduction

When a new strain of pathogen emerges, the first question asked is often whether existing vaccines might be effective against it. Experts have relied on examining the humoral immune response by using antibody assays to determine the potential of existing vaccines to cross-protect [1]. Immune responses to conserved T cell epitopes may result in reduced morbidity, despite the lack of cross-reactive antibody to the new strain [7,8,9]. This is supported by a case-controlled study that investigated the association of the pandemic IAV H1N1

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