Year: 2002
Type: conference-abstract
Abstract: The Haemagglutinin (HA) is the influenza surface glycoprotein that interacts with infectivity neutralizing antibodies.As a consequence of this immune pressure, it is the variable virus component important in the antigenic drift that results in recurrent epidemics of influenza.We have determined the crystallographic structure of three complexes formed between the Fab fragments of infectivity neutralizing antibodies and HA and the mechanism of neutralization of virus infectivity by these antibodies.In addition, measurements of the affinities for an antibody of mutants that escape neutralization by this antibody show that a 1000-fold affinity decrease is associated to escape from neutralization of infectivity.The antibodies, which are representative of the range of antibodies that react with haemagglutinin, differ in their sites of interaction with haemagglutinin and in their abilities to interfere in vitro with its two functions of receptor binding and membrane fusion.Two of them overlap with the receptor-binding site and block access to the site while the third is distant from this site.The three antibodies also differ in their abilities to prevent the structural transition of HA that is required for fusion of virus and cellular membranes, one of them blocks this transition, the other two do not.We demonstrate that despite these differences all three antibodies neutralize infectivity by preventing virus from binding to cells.Neutralization occurs at an average of one antibody bound per four haemagglutinins, a ratio sufficient to prevent the simultaneous receptor binding of haemagglutinins that is necessary to attach virus to cells.
Authors: P. Lukacik, J. Billington, A. Heinrich, K. Thurston, G. Smith, J. White, R. A. Smith, S. M. Lea
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1972579760