Engineering an HIV Envelope Protein to Activate Germline B Cell Receptors of Broadly Neutralizing VRC01-Class Antibodies

Background: The recent RV144 trial showed [similar]30% efficacy. Although the protection was modest, the trial indicated for the first time that a vaccine against HIV is possible. Immune correlate analysis suggests that the observed protection was due to nonneutralizing antibody responses. This efficacy might be improved if a vaccine could elicit broadly neutralizing antibodies (bNAbs). Of particular interest for vaccine design are the potent VRC01- class bNAbs targeting CD4 binding site on Env. Unfortunately, a number of studies have demonstrated that recombinant Env proteins do not bind germline-reverted VRC01 class Abs, indicating that current vaccine strategies using recombinant Env are unable to activate progenitor B cells that ultimately give rise to VRC01 class Abs.