Nabbing Broadly Neutralizing Antibodies from People with HIV Infection

In the advance online section of the Nature Medicine website, a group of researchers from the Vaccine Research Center at the National Institutes of Health report new findings suggesting that the induction of broadly neutralizing antibodies against HIV may be possible. The researchers evaluated the ability of serum sampled from a cohort of 32 HIV-infected individuals to neutralize a variety of HIV isolates from clades A, B & C. Sera from two individuals displayed broad neutralizing activity against most viruses tested. Further analyses revealed that these antibodies were directed against a conserved part of HIV's gp120 envelope protein that binds to the human CD4 molecule. Although additional work will be needed to try and home in on the specific epitope(s) that these antibodies are targeting, the researchers note that, encouragingly, "these data show that it is possible for B cells in the normal human repertoire to effectively target epitopes located in the gp120 CD4-binding site."

Nat Med. 2007 Aug 26; [Epub ahead of print]

Broad HIV-1 neutralization mediated by CD4-binding site antibodies.

Li Y, Migueles SA, Welcher B, Svehla K, Phogat A, Louder MK, Wu X, Shaw GM, Connors M, Wyatt RT, Mascola JR.

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

We have identified several patient sera showing potent and broad HIV-1 neutralization. Using antibody adsorption and elution from selected gp120 variants, the neutralizing specificities of the two most broadly reactive sera were mapped to the primary receptor CD4-binding region of HIV-1 gp120. Novel antibodies to the CD4-binding site are elicited in some HIV-1-infected individuals, and new approaches to present this conserved region of gp120 to the immune system may result in improved vaccine immunogens.