Zephyr Foundation

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 antibodies^{1, 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.
Correspondence to: This e-mail address is being protected from spambots. You need JavaScript enabled to view it ^1,5 Correspondence and requests for materials should be addressed to M.C.N.

Link: http://www.nature.com/nature/journal/vaop/ncurrent/abs/nature07930.html

Johannes F. Scheid^1,6, Hugo Mouquet¹, Niklas Feldhahn¹, Michael S. Seaman⁷, Klara Velinzon¹, John Pietzsch^1,8, Rene G. Ott², Robert M. Anthony², Henry Zebroski³, Arlene Hurley⁴, Adhuna Phogat⁹, Bimal Chakrabarti⁹, Yuxing Li⁹, Mark Connors¹⁰, Florencia Pereyra¹¹, Bruce D. Walker¹¹, Hedda Wardemann¹², David Ho¹³, Richard T. Wyatt⁹, John R. Mascola⁹, Jeffrey V. Ravetch² & Michel C. Nussenzweig^1,5

1. Laboratory of Molecular Immunology,
2. Laboratory of Molecular Genetics and Immunology,
3. Proteomics Resource Center,
4. Rockefeller University Hospital, and,
5. Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA
6. Charite Universitaetsmedizin, D-10117 Berlin, Germany
7. Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
8. Institute of Chemistry and Biochemistry, Freie Universität Berlin, D-14195 Berlin, Germany
9. Vaccine Research Center, and,
10. Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health Bethesda, Maryland 20892, USA
11. Partners AIDS Research Center, Mass General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
12. Max Planck Institute for Infection Biology, D-10117 Berlin, Germany
13. Aaron Diamond Aids Research Center; New York, New York 10065, USA