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

*Sea Lane Biotechnologies, 1455 Adams Drive, Menlo Park, CA 94025-1438;
^†Departments of Microbiology and Medicine, Mount Sinai School of Medicine One Gustave L. Levy Place, New York, NY 10029;
^‡Yüzüncü Yil University, Van TR-65200, Turkey; and
^¶Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037

Contributed by Richard A. Lerner, February 20, 2008 (received for review February 1, 2008)

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.

Footnotes

^§To whom correspondence may be addressed. E-mail: ramesh.bhatt{at}sealanebio.com or rlerner{at}scripps.edu
Author contributions: A.K.K., J.S., M.A.D., R.E.S., K.M.W., K.J.P., A.F., M.H., L.H., P.P., R.R.B., and R.A.L. designed research; A.K.K., J.S., M.A.D., R.E.S., K.M.W., K.J.P., A.F., P.P., and R.R.B. performed research; A.F.O. and M.I. contributed new reagents/analytic tools; M.H., L.H., and R.A.L. analyzed data; and A.K.K., M.H., L.H., R.R.B., and R.A.L. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0801367105/DCSupplemental.