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. 2008 Apr 22;105(16):5986-91.
doi: 10.1073/pnas.0801367105. Epub 2008 Apr 14.

Combinatorial antibody libraries from survivors of the Turkish H5N1 avian influenza outbreak reveal virus neutralization strategies

Arun K Kashyap  1 , John Steel, Ahmet F Oner, Michael A Dillon, Ryann E Swale, Katherine M Wall, Kimberly J Perry, Aleksandr Faynboym, Mahmut Ilhan, Michael Horowitz, Lawrence Horowitz, Peter Palese, Ramesh R Bhatt, Richard A Lerner
Affiliations

Combinatorial antibody libraries from survivors of the Turkish H5N1 avian influenza outbreak reveal virus neutralization strategies

Arun K Kashyap et al. Proc Natl Acad Sci U S A. .

Abstract

The widespread incidence of H5N1 influenza viruses in bird populations poses risks to human health. Although the virus has not yet adapted for facile transmission between humans, it can cause severe disease and often death. Here we report the generation of combinatorial antibody libraries from the bone marrow of five survivors of the recent H5N1 avian influenza outbreak in Turkey. To date, these libraries have yielded >300 unique antibodies against H5N1 viral antigens. Among these antibodies, we have identified several broadly reactive neutralizing antibodies that could be used for passive immunization against H5N1 virus or as guides for vaccine design. The large number of antibodies obtained from these survivors provide a detailed immunochemical analysis of individual human solutions to virus neutralization in the setting of an actual virulent influenza outbreak. Remarkably, three of these antibodies neutralized both H1 and H5 subtype influenza viruses.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
H5N1 antibodies from two survivors cross-react with HAs from H1N1 viruses. Bars are H5N1 Vietnam/1203/04 (dark gray), H5N1 Turkey/65596/06 (yellow), H5N1 Indonesia/5/05 (blue), H1N1 New Caledonia/20/99 (green), H1N1 South Carolina/1/18 (red), and H3N2 Wisconsin/67/05 (white).
Fig. 2.
Fig. 2.
The positions of H5 HA binding group 1 required and dominant mutations on the crystal structure of Fab 47e. Required (blue) and dominant (red) mutations from group 1 heavy chain sequences identified in H5 Vietnam/1203/2004 HA biopanning are superimposed on the crystal structure of the highly related anti-HIV Fab 47e. Mutations are shown in both backbone (Upper) and space-filling (Lower) models. A tight cluster is formed by four of the required mutations in, and adjacent to, CDR2.
See this image and copyright information in PMC

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