Structures of Broadly Neutralizing Anti-HIV Antibodies that Target the CD4 Binding Site on the HIV Envelope

Strategies to combat HIV require structural knowledge of how antibodies recognize HIV envelope proteins and how they are used by the immune system to eliminate viruses and virally-infected cells. A few years after infection, some HIV-infected patients develop broadly neutralizing antibodies (bNAbs), which neutralize across many HIV strains and confer protection against simian immunodeficiency virus (SIV) infection in non-human primates when delivered by passive immunization (i.e. purified Abs were injected). Despite the fact that HIV-infected individuals can produce bNAbs, a vaccine that can elicit such Abs has yet to be identified or designed. One problem in understanding how to elicit bNAbs is that the structural correlates of broad and potent neutralization of HIV are incompletely understood, largely due to the small number of purified and characterized human bNAbs available to researchers. Until recently, only a small number of bNAbs against HIV had been characterized. This issue was resolved by new methods for HIV antibody isolation from B cells of patients who produce high titers of broad neutralizing activity. Several of the antibodies recently isolated by Dr. Michel Nussenzweig’s laboratory, including NIH45-46, 3BNC117 and 3BNC60 [1], show superior potency and breadth to VRC01, previously th