Phase 1 Safety and Immunogenicity Evaluation of a Multiclade HIV-1 Candidate Vaccine Delivered by a Replication-Defective Recombinant Adenovirus Vector
Year of Publication
Catanzaro, AT; Koup, RA; Roederer, M; Bailer, RT; Enama, ME; Moodie, Z; Gu, L; Martin, JE; Novik, L; Chakrabarti, BK; Butman, B; Gall, J; King, C; Andrews, C; Sheets, R; Gomez, P; Mascola, J; Nabel, G; Graham, B; The Vaccine Research Center 006 Study Team
J Infect Dis
Adenoviruses; Adolescent Adult Antibodies; AIDS Vaccines/administration & dosage; CD8-Positive T-Lymphocytes/immunology; Human/genetics; T-Lymphocytes/immunology; Viral/blood Antibody Specificity Blotting; Western CD4-Positive
BACKGROUND: The development of an effective human immunodeficiency virus (HIV) vaccine is a high global priority. Here, we report the safety, tolerability, and immunogenicity of a replication-defective recombinant adenovirus serotype 5 (rAd5) vector HIV-1 candidate vaccine. METHODS: The vaccine is a mixture of 4 rAd5 vectors that express HIV-1 subtype B Gag-Pol fusion protein and envelope (Env) from subtypes A, B, and C. Healthy, uninfected adults were randomized to receive 1 intramuscular injection of placebo (n=6) or vaccine at dose levels of 10(9) (n=10), 10(10) (n=10), or 10(11) (n=10) particle units and were followed for 24 weeks to assess immunogenicity and safety. RESULTS: The vaccine was well tolerated but was associated with more reactogenicity at the highest dose. At week 4, vaccine antigen-specific T cell responses were detected in 28 (93.3%) and 18 (60%) of 30 vaccine recipients for CD4(+) and CD8(+) T cells, respectively, by intracellular cytokine staining assay and in 22 (73%) of 30 vaccine recipients by enzyme-linked immunospot assay. Env-specific antibody responses were detected in 15 (50%) of 30 vaccine recipients by enzyme-linked immunosorbant assay and in 28 (93.3%) of 30 vaccine recipients by immunoprecipitation followed by Western blotting. No neutralizing antibody was detected. CONCLUSIONS: A single injection induced HIV-1 antigen-specific CD4(+) T cell, CD8(+) T cell, and antibody responses in the majority of vaccine recipients. This multiclade rAd5 HIV-1 vaccine is now being evaluated in combination with a multiclade HIV-1 DNA plasmid vaccine.