Comprehensive maps of escape mutations from antibodies 10-1074 and 3BNC117 for Envs from two divergent HIV strains

Antibodies capable of neutralizing many strains of HIV are being explored as prophylactic and therapeutic agents, but viral escape mutations pose a major challenge. Efforts have been made to experimentally define the escape mutations from specific antibodies in specific viral strains, but it remains unclear how much the effects of mutations on neutralization differ among HIV strains. Here, we use pseudovirus deep mutational scanning to comprehensively map escape mutations from the V3 loop targeting antibody 10-1074 and the CD4-binding site targeting antibody 3BNC117 for both a clade A (BF520) and a clade B (TRO.11) HIV Envelope (Env). Mutations that escape neutralization by antibody 10-1074 are largely similar for the two Envs, but mutations that escape 3BNC117 differ greatly between Envs. Some differences in the effects of mutations on escape between Envs can be explained by strain-to-strain variation in mutational tolerance or potential N-linked glycosylation motifs, but other mutations have different effects on escape for unclear reasons. Overall, the extent to which measurements of mutational effects on antibody neutralization can be generalized across HIV strains differs among antibodies 10-1074 and 3BNC117.IMPORTANCEBroadly neutralizing antibodies are promising candidates as prophylactics and therapeutics for HIV. This study uses pseudoviruses to map all escape mutations for antibodies 10-1074 and 3BNC117 for the Envelope proteins from two different HIV strains. These maps can inform analyses of viral mutations observed in clinical trials and help understand how the escape mutations from these antibodies differ across HIV strains.