Extensively cross-reactive anti-HIV-1 neutralizing antibodies induced by gp140 immunization

doi:10.1073/pnas.0608635104

Extensively cross-reactive anti-HIV-1 neutralizing antibodies induced by gp140 immunization

Departments of *Preventive Medicine and Biometrics and
^†Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
^§GlaxoSmithKline Biologicals, B-1330 Rixensart, Belgium; and
^‡China Center for Disease Control and Prevention, Beijing 100050, China

Edited by Tilahun D. Yilma, University of California, Davis, CA, and approved May 4, 2007 (received for review October 2, 2006)

Abstract

An immunization regimen was evaluated in rabbits consisting of the soluble, oligomeric form of envelope glycoprotein of HIV-1, strain R2 (gp140_R2), or the surface component of the same envelope (Env), gp120_R2, in the adjuvant AS02A. The gp140_R2 was selected based on its unusual CD4-independent phenotype and the exceptionally broad neutralizing response in the infected donor. The gp140_R2 immunogen induced antibodies that achieved 50% neutralization of 48/48, and 80% neutralization of 43/46 primary strains of diverse HIV-1 subtypes tested. The strains tested included members of standard panels of subtype B and C strains, and other diverse strains known to be neutralization resistant. The gp120_R2 induced antibodies that neutralized 9/48 of the same strains. Neutralization was IgG-mediated and HIV-1-specific. These results demonstrate that induction of truly broad spectrum neutralizing antibodies is an achievable goal in HIV-1 vaccine development.

Footnotes

^¶To whom correspondence should be addressed at:
Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814.
E-mail: gquinnan{at}usuhs.mil
Author contributions: P.F.Z. and F.C. contributed equally to this work; P.F.Z., F.C., G.V., and G.V.Q. designed research; P.F.Z., F.C., M.D., A.C., P.B., Z.Z., Y.S., Y.-R.F., L.W., N.M., C.C.B., and G.V.Q. performed research; N.M., G.V., and G.V.Q. contributed new reagents/analytic tools; P.F.Z., F.C., M.D., A.C., C.C.B., and G.V.Q. analyzed data; and P.F.Z., F.C., C.C.B., and G.V.Q. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
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↵ ** Leroux-Roels, I., Clement, F., Leroux-Roels, G., Koutsoukos, M., Van Belle, P., Van Uffel, K., Vandepapelière, P., Hanon, E., Voss, G., Pedneault, L., AIDS Vaccine 2005 Conference, September 6–9, 2005, Montreal, QC, Canada, Abstr. 308.
This article contains supporting information online at www.pnas.org/cgi/content/full/0608635104/DC1.
Abbreviations:

Env,

envelope;

SHIV,

simian-human immunodeficiency virus.
Freely available online through the PNAS open access option.