Abstract

Current inactivated influenza vaccines provide protection when vaccine antigens and circulating viruses share a high degree of similarity in hemagglutinin protein. Five antigenic sites in the hemagglutinin protein have been proposed, and 131 amino acid positions have been identified in the five antigenic sites. In addition, 20, 18, and 32 amino acid positions in the hemagglutinin protein have been identified as mouse monoclonal antibody-binding sites, positively selected codons, and substantially diverse codons, respectively. We investigated these amino acid positions for predicting antigenic variants of influenza A/H3N2 viruses in ferrets. Results indicate that the model based on the number of amino acid changes in the five antigenic sites is best for predicting antigenic variants (agreement = 83%). The methods described in this study could be applied to predict vaccine-induced cross-reactive antibody responses in humans, which may further improve the selection of vaccine strains.

Highlights

  • Current inactivated influenza vaccines provide protection when vaccine antigens and circulating viruses share a high degree of similarity in hemagglutinin protein

  • Different cutoffs of amino acid changes in the HA1 polypeptide were evaluated for predicting antigenic variants

  • The highest agreement was found with a cutoff of >7 amino acid changes, which shows that the negative predictive value (NPV), Positive predictive value (PPV), and agreement were 66% (31/47), 81% (109/134), and 77% (140/181), respectively (Figure A)

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Summary

Introduction

Current inactivated influenza vaccines provide protection when vaccine antigens and circulating viruses share a high degree of similarity in hemagglutinin protein. Predicting Antigenic Variants The first model was based on amino acid differences in the whole HA1 polypeptide (329 residues). In addition to the amino acid change at position 247, A/Shanghai/11/87 had two more amino acid differences from A/Sichuan/2/87 (E156K, S186V) and A/Sydney/1/87 (A138S, N193K), but these three viruses were antigenically similar (antigenic distance

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