110 Hide and Seek: Evasion and Exposure of the HIV Envelope Peter D Kwong*, L Chen, C C Huang, S Majeed, G Ofek, and T Zhou Vaccine Res Ctr, NIAID, NIH, DHHS, Bethesda, MD, USA

The HIV envelope employs a variety of mechanisms to evade antibody neutralization.  But not all viral isolates nor all portions of the envelope are equally protected.  Two extremes are the V3 and the membrane-proximal regions, both of which are about 30 amino acids in size.  The V3 region appears designed to attract an immune response.  Neutralizing antibodies against the V3 region can be relatively easily elicited by immunization.  V3-reactive antibodies, however, typically neutralize only the more neutralization-sensitive fraction of primary isolates.  In contrast, the membrane-proximal region appears to be quite well hidden from the immune system.  Only three neutralizing antibodies have been characterized that react with this region.  These three, 2F5, 4E10, and Z13, are among the most broadly neutralizing antibodies against HIV-1 thus far isolated.  In order to gain an atomic-level understanding of the immunogenicity of the V3 and membrane-proximal regions, we have explored these two regions with X-ray crystallography.  Results and implications for vaccine design will be presented.