Antigenic structure of influenza virus haemagglutinin defined by hybridoma antibodies

Abstract

The recurrence of influenza virus infection in man is attributed primarily to changes occurring in the antigenic structure of the viral surface glycoproteins, especially of the haemagglutinin (HA) molecule. Comparative antigenic analysis of epidemic influenza virus strains has allowed the description of 'strain-specific' and 'cross-reactive' antigenic determinants. However, the interpretation of these findings remained ambiguous, because the specificity of the applied antisera was insufficiently defined and because the antigenic differences among the HA molecules of various epidemic virus strains resulted presumably from a large number of amino acid substitutions. Thus, in characterizing the antigenic structure of the HA molecule, our approach has been (1) to generate a panel of monoclonal anti-HA hybridoma antibodies, (2) to use some of these antibodies to select mutants of the influenza A/PR/8/34 (PR8) virus expressing antigenically altered HA molecules, and (3) to construct an operational antigenic map of the HA molecule by comparative antigenic analysis of the mutant viruses with the monoclonal antibodies. As we report here, analysis of the 34 mutant viruses selected has enabled us to define four antigenic sites on the HA molecule. Our observation that these sites have undergone antigenic drift to a different extent in nature implies that the mechanisms responsible for antigenic drift act selectively on distinct structures of the HA molecule.

Mapping of Antigenic Changes in the Haemagglutinin of Hong Kong Influenza (H3N2) Strains using a Large Panel of Monoclonal Antibodies

“…HK71 and Q70 were interesting in that they seem to have acquired a number of amino acid changes which place them ahead of their time. Gerhard et al (1981) have shown that uneven antigenic drift has also occurred among the antigenic sites of the HA of another influenza subtype (HON1) although they derive their conclusions in a different way. Work is in progress to produce panels of monoclonal antibodies against other members of the Hong Kong subtype in order to test the hypothesis that the position of emphasis of antibody pressure within the antigenic area of the haemagglutinin changes as the virus evolves.…”

Influenza Infection in Patients Before and After Liver Transplantation

“…Antigenic drift is believed to be driven by host immune selective pressure. 5 The course of influenza infection is usually quite rapid. Infection of the respiratory epithelium leads to viral replication within 4 to 6 hours and development of symptoms in 18 to 72 hours.…”

The production of monoclonal antibodies to rubella haemagglutinin and their use in antibody-capture assays for rubella-specific IgM

“…Small alterations in an antigen, such as are caused by single-point nucleotide deletions, may very significantly alter the avidity of a monoclonal antibody for the antigen (Gerhard et al 1981). Were these antibodies to be employed in the detection of infectious agents from clinical material this overspecificity may indeed have a profound effect on the success of such a technique, since it is increasingly apparent that a single pathogen, homogeneous when investigated by conventional serology, may in fact comprise a range of variants (Webster & Berton, 1981).…”