An Adjuvanted Polyprotein HIV-1 Vaccine Induces Polyfunctional Cross-Reactive CD4+ T Cell Responses in Seronegative Volunteers

overlapping peptide pools covering the 4 individual antigens. Results. Reactogenicity was higher during the 7-day period after each vaccine dose in the adjuvanted than in the nonadjuvanted groups. In the adjuvanted groups, the overall immune response rate was high after the second vaccine dose, with highest responder rates seen in the 10-lg F4/AS01 group (100% to 3 HIV-1 antigens and 80% to all 4 HIV-1 antigens). High and long-lasting CD4 1 T cell frequencies were observed (up to a median value of 1.2% F4-specific CD4 1 T cells at day 44), with strongest responses directed against reverse transcriptase. Antigen-specific CD4 1 T cells exhibited a polyfunctional phenotype, expressing at least CD40 ligand and interleukin 2, often in combination with tumor necrosis factor a and/or interferon c. Vaccine-induced CD4 1 T cell responses were broadly cross-reactive to all 4 antigens derived from HIV-1 clades A and C. Conclusions. These results support further clinical investigation of this HIV-1 vaccine candidate both in a prophylactic setting (alone, in conjunction with an envelope-based antigen or in combination with other vaccine approaches in a heterologous prime-boost regimen) and as a potentially disease-modifying therapeutic vaccine in HIV-1‐infected subjects. Clinical trials registration. NCT00434512.