Phase 1 Safety and Immunogenicity Evaluation of a Multiclade HIV-1 Candidate Vaccine Delivered by a Replication-Defective Recombinant Adenovirus Vector
12/2006
Journal Article
Authors:
Catanzaro, A.T.;
Koup, R.A.;
Roederer, M.;
Bailer, R.T.;
Enama, M.E.;
Moodie, Z.;
Gu, L.;
Martin, J.E.;
Novik, L.;
Chakrabarti, B.K.;
Butman, B.;
Gall, J.;
King, C.;
Andrews, C.;
Sheets, R.;
Gomez, P.;
Mascola, J.;
Nabel, G.;
Graham, B.;
Team, T.Vaccine Re
Secondary:
J Infect Dis
Volume:
194
Pagination:
1638-1649
URL:
http://www.ncbi.nlm.nih.gov/pubmed/17109335
Keywords:
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
Abstract:
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.
