Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning

Understanding the specificities of human serum antibodies that broadly neutralize HIV can inform prevention and treatment strategies. Here, we describe a deep mutational scanning system that can measure the effects of combinations of mutations to HIV envelope (Env) on neutralization by antibodies and polyclonal serum. We first show that this system can accurately map how all functionally tolerated mutations to Env affect neutralization by monoclonal antibodies. We then comprehensively map Env mutations that affect neutralization by a set of human polyclonal sera that neutralize diverse strains of HIV and target the site engaging the host receptor CD4. The neutralizing activities of these sera target different epitopes, with most sera having specificities reminiscent of individual characterized monoclonal antibodies, but one serum targeting two epitopes within the CD4-binding site. Mapping the specificity of the neutralizing activity in polyclonal human serum will aid in assessing anti-HIV immune responses to inform prevention strategies.

Automated summary

Understanding the specificities of human serum antibodies that neutralize HIV can inform prevention and treatment strategies. A deep mutational scanning system was developed to measure the effects of mutations to HIV envelope on antibody neutralization. The study found that different polyclonal serum show neutralizing activity against HIV by targeting various epitopes, similar to characterized monoclonal antibodies. Mapping the specificity of neutralizing activity in polyclonal serum will help in evaluating anti-HIV immune responses for prevention strategies.