Safety and immunogenicity of a Gag-Pol candidate HIV-1 DNA vaccine administered by a needle-free device in HIV-1-seronegative subjects.
OBJECTIVE
To evaluate the safety and immunogenicity of a candidate HIV DNA vaccine administered using a needle-free device.


METHODS
In this phase 1, dose escalation, double-blind, placebo-controlled clinical trial, 21 healthy adults were randomized to receive placebo or 0.5, 1.5, or 4 mg of a single plasmid expressing a Gag/Pol fusion protein. Each participant received repeat immunizations at days 28 and 56 after the first inoculation. Safety and immunogenicity data were collected.


RESULTS
The vaccine was well tolerated, with most adverse events being mild injection site reactions, including pain, tenderness, and erythema. No dose-limiting toxicities occurred. HIV-specific antibody response was not detected in any vaccinee by enzyme-linked immunosorbent assay. HIV-specific T-cell responses to Gag or Pol as measured by enzyme-linked immunospot assay and intracellular cytokine staining were of low frequency and magnitude.


CONCLUSIONS
This candidate HIV DNA vaccine was safe and well tolerated. No HIV-specific antibody responses were detected, and only low-magnitude HIV-specific T-cell responses were detected in 8 (53%) of 15 vaccinees. This initial product led to the development of a 4-plasmid multiclade HIV DNA Vaccine Research Center vaccine candidate in which envelope genes expressing Env from clades A, B, and C and a Nef gene from clade B have been added.
Tavel
Jorge A
JA
Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Martin
Julie E
JE
Kelly
Grace G
GG
Enama
Mary E
ME
Shen
Jean M
JM
Gomez
Phillip L
PL
Andrews
Charla A
CA
Koup
Richard A
RA
Bailer
Robert T
RT
Stein
Judy A
JA
Roederer
Mario
M
Nabel
Gary J
GJ
Graham
Barney S
BS
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D015750:Genes, gag; D015751:Genes, pol; D015483:HIV Antibodies / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D012449:Safety; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D016915:AIDS Vaccines; D015483:HIV Antibodies; D019444:Vaccines, DNA