Phase 1 Safety and Immunogenicity Evaluation of a Multiclade HIV-1 DNA Candidate Vaccine
Year of Publication
Graham, BS; Koup, RA; Roederer, M; Bailer, R; Enama, M; Moodie, Z; Martin, JE; McCluskey, MM; Chakrabarti, BK; Lamoreaux, L; Andrews, CA; Gomez, PL; Mascola, JR; Nabel, GJ; The Vaccine Research Center 004 Study Team
J Infect Dis
AIDS Vaccines; Antibodies Viral/blood; Antibody Specificity; Blotting Western; CD4-Positive T-Lymphocytes/immunology; CD8-Positive T-Lymphocytes/immunology; Cytokines/analysis/biosynthesis; Enzyme-Linked Immunosorbent Assay; Fusion Proteins
BACKGROUND: Gene-based vaccine delivery is an important strategy in the development of a preventive vaccine for acquired immunodeficiency syndrome (AIDS). Vaccine Research Center (VRC) 004 is the first phase 1 dose-escalation study of a multiclade HIV-1 DNA vaccine. METHODS: VRC-HIVDNA009-00-VP is a 4-plasmid mixture encoding subtype B Gag-Pol-Nef fusion protein and modified envelope (Env) constructs from subtypes A, B, and C. Fifty healthy, uninfected adults were randomized to receive either placebo (n=10) or study vaccine at 2 mg (n=5), 4 mg (n=20), or 8 mg (n=15) by needle-free intramuscular injection. Humoral responses (measured by enzyme-linked immunosorbant assay, Western blotting, and neutralization assay) and T cell responses (measured by enzyme-linked immunospot assay and intracellular cytokine staining after stimulation with antigen-specific peptide pools) were measured. RESULTS: The vaccine was well tolerated and induced cellular and humoral responses. The maximal CD4(+) and CD8(+) T cell responses occurred after 3 injections and were in response to Env peptide pools. The pattern of cytokine expression by vaccine-induced HIV-specific T cells evolved over time, with a diminished frequency of interferon- gamma -producing T cells and an increased frequency of interleukin-2-producing T cells at 1 year. CONCLUSIONS: DNA vaccination induced antibody to and T cell responses against 3 major HIV-1 subtypes and will be further evaluated as a potential component of a preventive AIDS vaccine regimen.