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 PG16, and membrane-proximal-binding antibodies like 2F5. 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. The V1/V2-directed antibodies are also attractive, as some estimate that this is the most commonly elicited broadly neutralizing response.

Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2012
Total Cost
$1,145,982
Indirect Cost
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