Inverse dose-response to gp140 YU2 foldon trimer formulated with aluminum phosphate and ISCOMATRIX® adjuvants

Background Conventional vaccine approaches based on delivery of HIV-1 envelope (Env) proteins or peptides derived from Env sequences have failed to generate broadly neutralizing antibodies (bNAbs) to the virus. Even with large doses (200 ug) of adjuvanted gp120 proteins administered multiple times to human volunteers, the subsequent antibody response boosts only moderately with each succeeding vaccination, and titers drop precipitously thereafter. We hypothesized that the usual practice of administering a moderate to high antigen doses may be counter productive to the goal of eliciting durable, high-affinity antibody responses. Methods