Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine.

Publication Type
Journal Article
Year of Publication
Graham, Barney S; Koup, Richard A; Roederer, Mario; Bailer, Robert T; Enama, Mary E; Moodie, Zoe; Martin, Julie E; McCluskey, Margaret M; Chakrabarti, Bimal K; Lamoreaux, Laurie; Andrews, Charla A; Gomez, Phillip L; Mascola, John R; Nabel, Gary J; Vaccine Research Center 004 Study Team
J Infect Dis
Date Published
2006 Dec 15
Adolescent; Adult; AIDS Vaccines; Antibodies, Viral; Antibody Specificity; Blotting, Western; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cytokines; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Fusion Proteins, gag-pol; Gene Products, nef; Genetic Vectors; HIV Infections; HIV-1; Humans; Immunization Schedule; Injections, Intramuscular; Male; nef Gene Products, Human Immunodeficiency Virus; Neutralization Tests; Plasmids; Vaccination; Vaccines, DNA; Viral Envelope 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.