Immunogenicity of Homologous and Heterologous Regimens of Ad26-Enva.01 and Ad35-Enva HIV Vaccines in HIV- Uninfected Volunteers in the U.S. and Africa
Background: Heterologous prime boost vaccine regimens offer a promising approach to improving T cell and antibody responses. Homologous and heterologous prime boost regimens were compared using two low seroprevalence Adenovirus vectors expressing two HIV-1 subtype A Envs. Methods: Ad26.EnvA.01 and/or Ad35-EnvA were administered at 5 · 10 10 viral particles intramuscularly in 217 volunteers (173 vaccine: 44 placebo) in three regions (US, East and South Africa) with two different intervals. US volunteers (Groups A-D) re- ceived heterologous (Ad26.EnvA.01 + Ad35-EnvA or Ad35- EnvA + Ad26.EnvA.01) regimens at 0/3- or 0/6-month intervals. African volunteers (Groups E-L) received the same heterologous regimens or homologous regimens consisting of two Ad26- EnvA.01 or two Ad35-EnvA at 0/3 months. Results: Vaccine regimens were well tolerated. IFN-gamma ELISPOT responses were detected in 44–100% of subjects (A-D), 6–62% (E-L) at 2 weeks and 78–100% (A-D), 47–88% (E-L) at 4 weeks after second vaccination for Ad26.EnvA.01 matched pep- tide pools and 11–75% (A-D), 0–69% (E-L) at 2 weeks and 33– 100% (A-D) and 0–87% (E-L) at 4 weeks for Ad35-Env A matched peptide pools. Env-specific CD4 and CD8 response rates were up to 70% (CD4) and 80% (CD8) for IFN-gamma and/or IL2 ex- pressing T-cells in Groups I-L (South Africa) at 4 weeks post second vaccination. T-cell response magnitudes by ELISPOT and flow cytometry were modest; differences between heterologous or homologous regimens were dependent on peptide sets. Env antibody responses were 93–100% in all groups with > 10-fold boost in magnitude at 4 weeks post second vaccination. Baseline and vaccine-elicited Ad26 and Ad35 neutralizing antibodies were observed with marked regional differences; East Africa > South Africa > US and Ad26 > Ad35 titers. Conclusion: Env antibody and T-cell responses were detected in all groups and no correlation was detected between baseline vector-specific neutralizing antibodies and Env-specific humoral or cellular immune responses across all regions. Immunogenicity in heterologous and homologous regimens was comparable.