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Antigenic variation in three distinct determinants of an influenza type A haemagglutinin molecule

Abstract

ALTHOUGH vaccines have been developed against many human viral pathogens, vaccination against influenza type A viruses has not been wholly successful. This is mainly due to the fact that the viral surface proteins, haemagglutinin and neuraminidase, are subject to antigenic evolution1. Major changes in antigenicity (antigenic shifts) are attributed to (1) the occasional occurrence of genetic reassortment between antigenically dissimilar influenza viruses, or (2) the re-introduction of a previously prevalent influenza virus into the human population. In contrast, minor antigenic variation (antigenic drift) is thought to result from spontaneous point mutations during virus replication followed by the selection of mutants in a partially immune host population. Antigenic drift in the haemagglutinin molecule is epidemiologically of greater importance than that in the neuraminidase molecule, probably because immune mechanisms neutralise virus through interaction with the haemagglutinin molecule. It seems, therefore, that a prerequisite of antigenic drift is a high mutation rate in the antigenic structures of the haemagglutinin molecule. In the present study, the frequency of antigenic mutant viruses present in cloned virus preparations was determined by means of monoclonal antibodies. It was found that antigenic changes in individual determinants of the haemagglutinin molecule of A/PR/8/34 (H0N1) occurred with an average frequency of 10−6 per infectious dose of virus and that the three determinants described here mutated independently of each other. The epidemiological significance of these observations is discussed.

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YEWDELL, J., WEBSTER, R. & GERHARD, W. Antigenic variation in three distinct determinants of an influenza type A haemagglutinin molecule. Nature 279, 246–248 (1979). https://doi.org/10.1038/279246a0

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