Sequential exposure to specific antibody escape mutations may program neutralization breadth during subtype A HIV-1 infection

Methods Here we characterized the initial nAb response in a subtype A HIV-1-infected Rwandan seroconverter and investigated how consequent immune events influenced the downstream development of cross-clade breadth. Autologous envelope (Env) glycoproteins from the transmitted/ founder virus and twenty longitudinal nAb escape variants were utilized to define the neutralization targets of autologous plasma and monoclonal antibodies (mAbs), the latter of which were also examined genetically and structurally through crystallization. Heterologous Env glycoproteins from nine cross-clade variants were used to determine neutralization breadth.