AS01B-, MF59-, and alum-based adjuvants and HIV vaccine immunogenicity: a post-hoc cross-protocol comparison of results from HVTN 100, 107, 120, and 702

Introduction Vaccine adjuvants are crucial in HIV vaccine development, enhancing immune responses. Immune responses generated by different adjuvanted vaccines are rarely compared directly with the same vaccine antigens. Methods This retrospective cross-protocol, cross-sectional analysis examined four randomized, controlled, double-blinded, multicenter trials (HVTN 100, 107, 120, and 702) of adults without HIV who received the ALVAC-HIV (vCP2438) vaccine and a bivalent gp120 protein booster with either MF59, Alum, or AS01 B adjuvant. Participants received ALVAC-HIV at months 0, 1, 3, 6, and 12, and the adjuvanted protein at months 3, 6, and 12. Data from month 6.5 were compared for IgG V1V2 binding antibodies (bAb) and CD4+ T-cell responses, measured as IFN-γ and/or IL-2 expression, using Wilcoxon and Barnard’s tests with FDR p-value multiplicity adjustment. Reactogenicity and adverse event profiles were also assessed. Results AS01 B elicited higher CD4+ T cell magnitudes among positive responders than either MF59 or Alum adjuvant to the 3 antigens considered: 1086, TV1, ZM96. No statistically significant differences were observed between MF59 and Alum in CD4+ T-cell responses. Regarding IgG bAb responses, AS01 B induced significantly higher magnitudes among positive responders compared to both MF59 and Alum for the C.1086C V1V2 and Con 6 gp120/B antigens. Additionally, AS01 B elicited greater IgG bAb responses than MF59 for gp70-96ZM651.02 V1V2 and gp70_B.CaseA V1V2, although no significant differences were found between AS01 B and Alum for these antigens. AS01 B also showed a trend toward greater reactogenicity, though this difference did not reach statistical significance. Importantly, no serious adverse events occurred in any of the groups. Conclusion The AS01 B adjuvant demonstrated superior IgG binding antibody and CD4+ T-cell responses compared with MF59 and Alum, when given with gp120 protein boost after ALVAC-HIV prime. These findings support AS01 B as a superior adjuvant for HIV vaccine development, relative to MF59 and Alum.