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Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals

Nature volume 458, pages 636–640 (2009)Cite this article

Abstract

Antibodies to conserved epitopes on the human immunodeficiency virus (HIV) surface protein gp140 can protect against infection in non-human primates, and some infected individuals show high titres of broadly neutralizing immunoglobulin (Ig)G antibodies in their serum. However, little is known about the specificity and activity of these antibodies1,2,3. To characterize the memory antibody responses to HIV, we cloned 502 antibodies from HIV envelope-binding memory B cells from six HIV-infected patients with broadly neutralizing antibodies and low to intermediate viral loads. We show that in these patients, the B-cell memory response to gp140 is composed of up to 50 independent clones expressing high affinity neutralizing antibodies to the gp120 variable loops, the CD4-binding site, the co-receptor-binding site, and to a new neutralizing epitope that is in the same region of gp120 as the CD4-binding site. Thus, the IgG memory B-cell compartment in the selected group of patients with broad serum neutralizing activity to HIV is comprised of multiple clonal responses with neutralizing activity directed against several epitopes on gp120.

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Figure 1: Anti-gp140 antibody cloning.
Figure 2: Anti-gp140 antibody repertoire.
Figure 3: Anti-gp140 mapping by ELISA.
Figure 4: Neutralizing activity.

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Acknowledgements

We thank D. Wycuff, E. Lybarger and B. Dey for supplying gp120 proteins for mapping studies, K. McKee for serum adsorption studies and N. Doria-Rose for her work with patient material from patients 4 and 6. This research was supported by the Rockefeller University, the International Aids Vaccine Initiative, the Bill and Melinda Gates Foundation, the Intramural Research Program of the Vaccine Research Center (R.T.W., J.R.M.), and the Division of Intramural Research (M.C.), National Institute of Allergy and Infectious Diseases, National Institutes of Health. J.F.S. was supported by the Deutscher Akademischer Austauschdienst, H.M. was supported by the Fondation Recherche Médicale. M.C.N. is a Howard Hughes Medical Institute investigator.

Author information

Authors and Affiliations

  1. Laboratory of Molecular Immunology,,

    Johannes F. Scheid, Hugo Mouquet, Niklas Feldhahn, Klara Velinzon, John Pietzsch & Michel C. Nussenzweig

  2. Laboratory of Molecular Genetics and Immunology,,

    Rene G. Ott, Robert M. Anthony & Jeffrey V. Ravetch

  3. Proteomics Resource Center,,

    Henry Zebroski

  4. Rockefeller University Hospital, and,,

    Arlene Hurley

  5. Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA ,

    Michel C. Nussenzweig

  6. Charite Universitaetsmedizin, D-10117 Berlin, Germany

    Johannes F. Scheid

  7. Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA ,

    Michael S. Seaman

  8. Institute of Chemistry and Biochemistry, Freie Universität Berlin, D-14195 Berlin, Germany

    John Pietzsch

  9. Vaccine Research Center, and,,

    Adhuna Phogat, Bimal Chakrabarti, Yuxing Li, Richard T. Wyatt & John R. Mascola

  10. Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health Bethesda, Maryland 20892, USA ,

    Mark Connors

  11. Partners AIDS Research Center, Mass General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA ,

    Florencia Pereyra & Bruce D. Walker

  12. Max Planck Institute for Infection Biology, D-10117 Berlin, Germany

    Hedda Wardemann

  13. Aaron Diamond Aids Research Center,

    David Ho

  14. New York, New York 10065, USA

    David Ho

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  1. Johannes F. Scheid
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Correspondence to Michel C. Nussenzweig.

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This file contains Supplementary Methods, a Supplementary Reference, Supplementary Figures 1-10 with Legends and Supplementary Tables 1-6. (PDF 1254 kb)

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Scheid, J., Mouquet, H., Feldhahn, N. et al. Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature 458, 636–640 (2009). https://doi.org/10.1038/nature07930

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