title: Excellent safety and tolerability of the human immunodeficiency virus type 1 pGA2/JS2 plasmid DNA priming vector vaccine in HIV type 1 uninfected adults.
abstract: A vaccine consisting of DNA priming followed by recombinant modified vaccinia Ankara (rMVA) boosting has achieved long-term control of a pathogenic challenge with a chimera of simian and human immunodeficiency viruses (SHIV-89.6P) in rhesus macaques. Based on these results, clade B HIV-1 DNA and rMVA immunogens have been developed for trials in humans. We conducted a first-time in humans phase I safety trial using the pGA2/JS2 (JS2) HIV-1 DNA priming vector expressing Gag, Pol, Env, Tat, Rev, and Vpu. Thirty HIV-uninfected adults were vaccinated with 0.3 or 3 mg of JS2 DNA, or a saline placebo, by intramuscular injection at months 0 and 2. Both doses of DNA were safe and well-tolerated with no differences between the control, 0.3 mg, or 3 mg groups (n = 6, 12, and 12, respectively) through 12 months of postvaccination follow- up. A chromium-release assay using fresh peripheral blood mononuclear cells (PBMCs) and a validated IFN-gamma ELISpot assay with frozen PBMCs failed to detect CD4(+) or CD8(+) HIV-1-specific T cell responses. HIV-specific neutralizing antibodies were also not detected. The vaccine is being further developed as a priming vector for a combined DNA plus rMVA prime/boost HIV vaccination regimen.
authors.affiliation: University of Alabama at Birmingham, USA. mmulli2@emory.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: Mulligan
authors.forename: N D
authors.initials: ND
authors.lastname: Russell
authors.forename: C
authors.initials: C
authors.lastname: Celum
authors.forename: J
authors.initials: J
authors.lastname: Kahn
authors.forename: E
authors.initials: E
authors.lastname: Noonan
authors.forename: D C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: G
authors.initials: G
authors.lastname: Ferrari
authors.forename: K J
authors.initials: KJ
authors.lastname: Weinhold
authors.forename: J M
authors.initials: JM
authors.lastname: Smith
authors.forename: R R
authors.initials: RR
authors.lastname: Amara
authors.forename: H L
authors.initials: HL
authors.lastname: Robinson
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects* / Q000276:immunology; D000328:Adult; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors / Q000009:adverse effects / Q000276:immunology; D015483:HIV Antibodies / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D010957:Plasmids / Q000009:adverse effects* / Q000276:immunology; D018709:Statistics, Nonparametric; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000009:adverse effects* / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D019444:Vaccines, DNA; D007371:Interferon-gamma