Engineered gp120 immunogens that elicit VRC01-like antibodies by vaccination

Abstract

Background: One of the great challenges for an HIV vaccine is to elicit broadly neutralizing antibodies specific for conserved epitopes from which the virus cannot easily escape. The CD4 binding site is one such epitope against which several antibodies (e.g. b12, VRC01) have been isolated. In macaques infected with SHIV, passive immunization with these CD4-directed neutralizing antibodies fails to control the virus, but prophylactic administration is highly protective. Similarly, patients who generate neutralizing antibodies over the course of an HIV infection derive no clinical benefit from them, but eliciting such antibodies prophylactically by vaccination may prevent the virus from establishing its lethal foothold.