Journal Article

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

Nussenzweig, Michel C., Ho, David, Mouquet, Hugo, Connors, Mark, Anthony, Robert M., Ravetch, Jeffrey V., Velinzon, Klara, Feldhahn, Niklas, Scheid, Johannes F., Mascola, John R., Ott, Rene G., Wyatt, Richard T., Walker, Bruce D., Seaman, Michael S., Li, Yuxing, Phogat, Adhuna, Hurley, Arlene, Pereyra, Florencia, Pietzsch, John, Chakrabarti, Bimal, Wardemann, Hedda, Zebroski, Henry

2009

Overview

Multiple antibodies fight HIV Serologic memory is an important factor in long-term vaccine efficacy, but there is little understanding of the antibodies produced by memory B cells in individuals infected with important human pathogens such as HIV. To examine the memory antibody response to HIV, Scheid et al . cloned more than 500 antibodies from HIV-specific memory B cells from six HIV-infected patients with high serum titres of broadly neutralizing antibodies. The B-cell memory response to HIV in these patients was composed of up to 50 independent expanded B clones expressing a heterogeneous collection of antibodies to different viral epitopes, several of which may be important for broad HIV neutralization and effective vaccination. This study clones and characterizes antibodies present in six HIV-infected subjects with low-to-intermediate viral loads. 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Antibody Affinity / B cells / B-Lymphocytes - immunology / Binding Sites / Biological and medical sciences / CD4 Antigens - metabolism / Competition / Control / env Gene Products, Human Immunodeficiency Virus - chemistry / env Gene Products, Human Immunodeficiency Virus - immunology / env Gene Products, Human Immunodeficiency Virus - metabolism / Enzyme-Linked Immunosorbent Assay / Epitope Mapping / Epitopes, B-Lymphocyte - chemistry / Epitopes, B-Lymphocyte - immunology / Gene expression / HIV / HIV antibodies / HIV Antibodies - analysis / HIV Antibodies - immunology / HIV Antibodies - isolation & purification / HIV Envelope Protein gp120 - chemistry / HIV Envelope Protein gp120 - immunology / HIV Envelope Protein gp120 - metabolism / HIV Envelope Protein gp41 - chemistry / HIV Envelope Protein gp41 - immunology / HIV infection / HIV Infections - immunology / Human immunodeficiency virus / Human viral diseases / Humanities and Social Sciences / Humans / Immune serums / Immunization / Immunodeficiencies / Immunodeficiencies. Immunoglobulinopathies / Immunologic Memory - immunology / Immunopathology / Infectious diseases / letter / Medical sciences / Monoclonal antibodies / multidisciplinary / Neutralization Tests / Primates / Receptors, HIV - metabolism / Research centers / Science / Science (multidisciplinary) / Viral diseases / Viral diseases of the lymphoid tissue and the blood. Aids / Viral Load