Influence of the amino acid differences between the hemagglutinin HA1 domains of influenza virus H1N1 strains on their reaction with antibody

For influenza H1N1 strains, including some of their escape variants, the as sociation of amino acid differences located at their hemagglutinin HA1 doma ins with their antigenic relationship was examined. The antigenic relations hip was recorded in terms of the ratios of hemagglutination inhibition (HI) titers, the concentration of antibody molecules recognized by the virus, a nd the equilibrium constant of epitope-paratope interaction determined with heterologous virus compared to that found with homologous virus. The HI ti ters of antisera were found to depend primarily on the concentration of ant ibody molecules recognized by the virus and much less on the equilibrium co nstants. The avidity of antibody in sera raised against historically later strains with earlier strains was higher than vice verse. In contrast to the results obtained with antisera, the same concentration of monoclonal antib ody directed to the Sb site of A/Brazil virus was recognized by both hetero logous and homologous viruses, and the differences in HI titers observed we re due to avidity changes only. Some of the amino acid differences located at each of the antigenic sites were found to be associated with a reduction in the HI titers and in the concentration of antibody molecules recognized by heterologous virus, whereas other differences in addition decreased the avidity of epitope-paratope interaction. Further amino acid differences de creased the avidity only. The strains tested differed also in their amino a cids located outside the antigenic sites. However, an influence of these di fferences on the reaction of virus with antibody could not be evidenced. Fo r the strains tested, the antigenic hemagglutinin drift occurred by reducti on of the concentration of antibody molecules recognized by the virus and b y avidity changes, which, in turn, were caused by exchanges of some key res idues located at the antigenic sites. (C) 1999 Wiley-Liss, Inc.