Wednesday, June 20, 2007 - 9:45 AM
Cottonwoods (Boise Centre on the Grove)

HIV Envelope: Pursuing A Moving Target For Vaccine Design

Wendy Blay1, Theresa Kasprzyk2, and Nancy L. Haigwood1. (1) Seattle Biomedical Research Institute, Seattle, WA, (2) University of Washington, Seattle, WA

The quest for an HIV vaccine has proven challenging on a number of levels: the immune correlates of control are not fully understood, the virus undergoes rapid evolution, and HIV is exceptionally adept at immune evasion. It is believed that broad, cross-reactive neutralizing antibodies (NAbs) will be an important component of an effective HIV vaccine. As the only viral protein present on the surface of the virion, Envelope is the sole target of NAbs against HIV. The handful of neutralizing epitopes shared by multiple isolates of HIV are well concealed by large variable loops, recessed pockets, and carbohydrates that are able to add, remove, and rearrange in an evolving glycan shield. In contrast, the exposed epitopes are highly variable and typically isolate specific. An important question that remains unanswered lies in the boundaries of variation that exist as the virus evolves and the relationship between these changes and NAbs.

A longitudinal analysis using a macaque model of infection revealed a remarkable degree of conservation in HIV Envelope glycosylation and consistent patterns of change that occur in a small number of carbohydrates proximal to the CD4 receptor binding site. The majority of viral variants that undergo these carbohydrate changes are able to escape a broad modality of neutralizing agents. A cross-sectional analysis of published HIV sequences suggests similar hotspots of glycosylation change. These data help to illuminate possible commonalities in mechanisms of viral escape from NAbs and may aid the design of vaccines that could potentially circumvent such changes.