A phase 1 study to evaluate the safety and immunogenicity of a recombinant HIV type 1 subtype C adeno-associated virus vaccine.
A novel prophylactic AIDS vaccine candidate, consisting of single-stranded DNA for HIV-1 subtype C gag, protease, and part of reverse transcriptase genes, enclosed within a recombinant adeno-associated virus serotype-2 protein capsid (tgAAC09) induced T cell responses and antibodies in nonhuman primates. In this randomized, dose escalation phase I trial, HIV-uninfected healthy volunteers (50 in Europe, 30 in India) received a single intramuscular injection of tgAAC09 at 3 x 10(9) DNase resistant particles (DRP) (n = 16), 3 x 10(10) DRP (n = 23), 3 x 10(11) DRP (n = 25), or placebo (n = 16). Twenty-one participants in Europe received a second (boost) dose of 3 x 10(11) DRP tgAAC09 or placebo at least 24 weeks after the first injection. The vaccine was safe and well-tolerated after initial and boost vaccination. Local and systemic reactogenicity was experienced by 13-25% of participants and was not dose related. No vaccine-related serious adverse events were reported. Modest HIV-specific T cell responses were detected in 7/64 vaccinees (40-385 SFC/10(6) PBMC), with 16% (4/25) responders in the highest dose group. All responses were to Gag epitopes. tgAAC09 appears to be safe, well-tolerated, and modestly immunogenic. Further evaluation of higher doses of tgAAC09 and boost injections is ongoing in Africa.
National AIDS Research Institute, Pune, India.
Sanjay
S
Mehendale
Jan
J
van Lunzen
Nathan
N
Clumeck
Jurgen
J
Rockstroh
Eva
E
Vets
Philip R
PR
Johnson
Pervin
P
Anklesaria
Burc
B
Barin
Mark
M
Boaz
Sonali
S
Kochhar
Jennifer
J
Lehrman
Claudia
C
Schmidt
Mathieu
M
Peeters
Carolynne
C
Schwarze-Zander
Kabeya
K
Kabamba
Tobias
T
Glaunsinger
Seema
S
Sahay
Madhuri
M
Thakar
Ramesh
R
Paranjape
Jill
J
Gilmour
Jean-Louis
JL
Excler
Patricia
P
Fast
Alison E
AE
Heald
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000917:Antibody Formation; D002213:Capsid / Q000276:immunology; D004279:DNA, Viral / Q000008:administration & dosage; D000229:Dependovirus / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D022721:Vaccines, Virosome / Q000008:administration & dosage* / Q000009:adverse effects; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
D016915:AIDS Vaccines; D004279:DNA, Viral; D019444:Vaccines, DNA; D022721:Vaccines, Virosome; D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma