Centralized HIV-1 envelope immunogens and neutralizing antibodies.

Centralized HIV-1 genes (consensus, most recent common ancestor and center of the tree) have recently been explored for induction of broadly reactive immune responses to overcome the extraordinary genetic diversity among HIV-1 strains. Although all of these strategies are based on artificial sequences predicted by computer programs, they retain biological function, and use the CCR5 co-receptor for entry into target cells as transmitted HIV-1 Envs. Results from laboratory animals indicate that centralized immunogens are superior to many wild-type immunogens for inducing cross-subtype T and B cell immune responses. Structural modifications have improved the ability of consensus Envs to elicit antibody responses that neutralize a spectrum of HIV-1 Env pseudoviruses. However, the more difficult to neutralize tier 2 Env pseudoviruses are generally not neutralized well by anti-consensus Env antibodies, indicating the need for further modifications, new formulations, or additional strategies to generate antibodies that neutralize a full spectrum of transmitted HIV-1 strains.