The epitope regions of H1-subtype influenza A, with application to vaccine efficacy

Abstract

The recent emergence of H1N1 (swine flu) illustrates the ability of the influenza virus to create antigens new to the human immune system, even within a given hemagglutinin and neuraminidase subtype. This new H1N1 strain is sufficiently distinct, for example, from the A/Brisbane/59/2007 (H1N1)-like virus strain of influenza in the 2008/09 Northern hemisphere vaccine that protection is not expected to be substantial. The human immune system responds primarily to the five epitope regions of the hemagglutinin protein. By determining the fraction of amino acids that differ between a vaccine strain and a viral challenge strain in the dominant epitope regions, a measure of antigenic distance that correlates with epidemiological studies of H3 influenza A vaccine efficacy in humans with R2 = 0.81 is derived. This measure of antigenic distance is called pepitope. The relation between vaccine efficacy and pepitope is given by E = 0.47 – 2.47 × pepitope. We here identify the epitope regions of H1 hemagglutinin, so that vaccine efficacy may be reliably estimated for H1N1 influenza A.