Antigenicity-defined conformations of an extremely neutralization-resistant HIV-1 envelope spike

Significance A vaccine against HIV-1 should elicit antibodies that prevent infection (“neutralize”) by binding the viral envelope glycoprotein (Env). The extraordinary genetic diversity of Env means that protective antibodies must recognize one of a few broadly conserved sites (“epitopes”). The trimeric Env protein fluctuates among a range of conformations: Closed conformations expose only the conserved epitopes, whereas various open conformations expose many other, more variable epitopes. The latter dominate immune responses and restrict protection to a narrow range of viral strains. We describe here the properties of Env from an extremely neutralization-resistant HIV-1 variant. We find that it binds only antibodies that recognize conserved epitopes, consistent with a tightly closed conformation, and suggest that it might be a suitable vaccine template.