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© Research
Publication : Journal of virology

Anti-gp41 antibodies cloned from HIV-infected patients with broadly neutralizing serologic activity

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of virology - 10 Mar 2010

Pietzsch J, Scheid JF, Mouquet H, Seaman MS, Broder CC, Nussenzweig MC

Link to Pubmed [PMID] – 20219932

J. Virol. 2010 May;84(10):5032-42

Most HIV-infected individuals develop antibodies to the gp120 and gp41 components of the viral spike; however, only a fraction of these individuals mount a broadly neutralizing serum response against HIV. We have cloned anti-HIV antibodies from the memory B-cell compartment of six individuals with variable viral loads and high titers of broadly neutralizing antibodies. Here, we report on the features of the anti-gp41 response in these patients. Competition experiments with previously characterized antibodies targeting defined epitopes on the gp41 ectodomain showed antibodies directed against the “immunodominant region” (cluster I), the carboxy-terminal heptad repeat (cluster II), and the membrane-proximal external region (cluster IV). On the other hand, antibodies directed against the amino-terminal part of the molecule, including the fusion peptide, polar region, and the N-terminal heptad repeat, were not detected. When all patients’ data were combined, unique B-cell clones targeting cluster I, II, and IV accounted for 32%, 49%, and 53% of all anti-gp41-reactive B cells, respectively; therefore, no single region was truly immunodominant. Finally, although we found no new neutralizing epitopes or HIV-1-neutralizing activity by any of the gp41 antibodies at concentrations of up to 50 microg/ml, high concentrations of 7 out of 15 anti-cluster I antibodies neutralized tier 2 viruses.

http://www.ncbi.nlm.nih.gov/pubmed/20219932