Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine.
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.
Graham
Barney S
BS
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-3017, USA. bgraham@mail.nih.gov
Koup
Richard A
RA
Roederer
Mario
M
Bailer
Robert T
RT
Enama
Mary E
ME
Moodie
Zoe
Z
Martin
Julie E
JE
McCluskey
Margaret M
MM
Chakrabarti
Bimal K
BK
Lamoreaux
Laurie
L
Andrews
Charla A
CA
Gomez
Phillip L
PL
Mascola
John R
JR
Nabel
Gary J
GJ
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000918:Antibody Specificity; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000276:immunology; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D007273:Injections, Intramuscular; D008297:Male; D009500:Neutralization Tests; D010957:Plasmids; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D016207:Cytokines; D015685:Fusion Proteins, gag-pol; D015693:Gene Products, nef; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus