title: Evolution in the influenza A H3 stalk - a challenge for broad-spectrum vaccines?
abstract: Recently, a number of broad-spectrum human antibodies binding to the stalk region of influenza A haemagglutinin (HA) have been isolated. As this region tends to develop substitutions at a slower rate than other regions of HA, a vaccine eliciting such antibodies could have a longer effective life. But this begs a question: is the stalk resistant to change even in the face of evolutionary pressure? In this paper, we analysed the known epitopes in the H3 stalk and, utilizing a collection of 3440 sequences, present a novel approach for detecting putative B-cell epitopes in regions such as this, in which mutations occur infrequently. We concluded that there have been periods of activity in the stalk that are consistent with the evolution of antigenic escape. This work casts light on the presence of stalk-binding antibodies in the population as a whole and, through the analysis of antigenically active regions in the stalk, may contribute to the identification of epitopes that are refractive to change and hence useful for vaccine development.
authors.affiliation: Institute of Structural and Molecular Biology and Department of Biological Sciences, Birkbeck College, University of London, UK.
authors.forename: William D
authors.initials: WD
authors.lastname: Lees
authors.affiliation: Institute of Structural and Molecular Biology and Department of Biological Sciences, Birkbeck College, University of London, UK.
authors.forename: David S
authors.initials: DS
authors.lastname: Moss
authors.affiliation: Institute of Structural and Molecular Biology and Department of Biological Sciences, Birkbeck College, University of London, UK.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Shepherd
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology; D019295:Computational Biology; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D019143:Evolution, Molecular; D014644:Genetic Variation; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control / Q000821:virology*; D017422:Sequence Analysis, DNA
chemical_list: D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines