Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 candidate vaccine delivered by a replication-defective recombinant adenovirus vector.

Publication Type
Journal Article
Year of Publication
Catanzaro, Andrew T; Koup, Richard A; Roederer, Mario; Bailer, Robert T; Enama, Mary E; Moodie, Zoe; Gu, Lin; Martin, Julie E; Novik, Laura; Chakrabarti, Bimal K; Butman, Bryan T; Gall, Jason G D; King, C Richter; Andrews, Charla A; Sheets, Rebecca; Gomez, Phillip L; Mascola, John R; Nabel, Gary J; Graham, Barney S; Vaccine Research Center 006 Study Team
J Infect Dis
Date Published
2006 Dec 15
Adenoviruses, Human; Adolescent; Adult; AIDS Vaccines; Antibodies, Viral; Antibody Specificity; Blotting, Western; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cytokines; Dose-Response Relationship, Immunologic; Double-Blind Method; env Gene Products, Human Immunodeficiency Virus; Enzyme-Linked Immunosorbent Assay; Female; Flow cytometry; Fusion Proteins, gag-pol; Gene Products, env; Genetic Vectors; HIV Infections; HIV-1; Humans; Injections, Intramuscular; Male; Nausea; Recombination, Genetic; Vaccination; Vaccines, Synthetic

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.