Structural and functional basis for broad spectrum neutralization of avian and human influenza A virus infection

SUI, J; PÉREZ, S; WEI, G; AIRD, D; CHEN, L; SANTELLI, E; STEC, B; CADWELL, G; ALI, M; MURAKAMI, A; YAMMANURU, A; HAN, T; COX, N; BANKSTON, L; DONIS, R; LIDDINGTON, R; MARASCO, W

NATURE STRUCT. BIOL.

Nature Publishing Group

Año: 2009 vol. 16 p. 265 - 273

1072-8368

Influenza virus remains a serious health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Here we used a human non-immune antibody phage-display library and the H5 hemagglutinin ectodomain to select ten neutralizing antibodies (nAbs) that were effective against all group 1 influenza viruses tested, including H5N1 ´bird flu´ and the H1N1 ´Spanish flu´. The crystal structure of one such nAb bound to H5 shows that it blocks infection by inserting its heavy chain into a conserved pocket in the stem region, thus preventing membrane fusion. Nine of the nAbs employ the germline gene VH1-69, and all seem to use the same neutralizing mechanism. Our data further suggest that this region is recalcitrant to neutralization escape and that nAb-based immunotherapy is a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.