Characterizing the fitness cost of viral escape from the HIV-1 broadly neutralizing monoclonal antibody VRC01

Background The receptor-binding site on the HIV glycoprotein gp120 is a highly conserved epitope, and certain antibodies directed against this CD4 binding site (CD4bs) can potently neutralize the majority of circulating HIV-1 isolates. One such antibody, VRC01, was isolated from a slow progressor HIV-1 infected donor who maintained low to moderate viral load without treatment. We recently described that almost all viruses in this donor plasma had escaped VRC01 neutralization. This raised the question of whether viral escape from a broadly reactive CD4bs antibody results in reduced affinity for CD4 and thus, a fitness cost to viral replication.