Excellent safety and tolerability of the human immunodeficiency virus type 1 pGA2/JS2 plasmid DNA priming vector vaccine in HIV type 1 uninfected adults.
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.
Mulligan
M J
MJ
University of Alabama at Birmingham, USA. mmulli2@emory.edu
Russell
N D
ND
Celum
C
C
Kahn
J
J
Noonan
E
E
Montefiori
D C
DC
Ferrari
G
G
Weinhold
K J
KJ
Smith
J M
JM
Amara
R R
RR
Robinson
H L
HL
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*
D016915:AIDS Vaccines; D015483:HIV Antibodies; D019444:Vaccines, DNA; D007371:Interferon-gamma