Neutralization Mechanisms Of Anti-HIV-1 Monoclonal Antibodies

National Institute Of Allergy And Infectious Diseases

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Abstract

A lack of neutralizing antibodies distinguishes HIV-1 from most other viral pathogens and is responsible to a large degree for the ability of HIV-1 to maintain a persistent infection. A few monoclonal antibodies have been isolated that are broadly neutralizing. We have used X-ray crystallography to investigate the epitopes of broadly neutralizing antibodies and their mechanisms of neutralization. In particular, we have examined CD4-binding-site directed antibodies like VRC01, V1/V2-directed antibodies like PG9 and CAP256-VRC26, membrane-proximal-binding antibodies like 2F5 and 10E8, and gp120-gp41 reactive antibodies like 35O22. The VRC01 antibody is particularly attractive as it neutralizes over 90% of circulating HIV-1 isolates and appears to be elicited in high titer in 5-10% of HIV-1 infected individuals; however its uncommon development make its elicitation problematic. The V1/V2-directed and V3-glycan antibodies are also attractive, as some estimate that these are the most commonly elicited broadly neutralizing responses. Antibodies against the membrane-proximal region of HIV-1 are also attractive, as this region is highly conserved and recognition does not involve N-linked glycan. Last, recently identified antibodies against gp120-gp41 epitopes such as 35O22, 8ANC151, and PGT151 are providing to be commonly elicited and/or highly potent.