title: A phase 2 study to evaluate the safety and immunogenicity of a recombinant HIV type 1 vaccine based on adeno-associated virus.
abstract: The recombinant vaccine, tgAAC09, based on an adeno-associated virus serotype 2 (AAV2) vector encoding HIV-1 subtype C Gag, protease, and part of reverse transcriptase, induced robust T cell and antibody responses in nonhuman primates. In a previous phase I study in 80 healthy HIV-seronegative European and Indian adults, the vaccine was generally safe, well tolerated, and modestly immunogenic when administered once at doses up to 3 x 10(11) DRP. This phase II double-blind, randomized, placebo-controlled trial tested two administrations and a higher dosage of tgAAC009. Ninety-one healthy HIV-seronegative adults from three African countries were given one of three dosage levels of tgAAC09 (3 x 10(10), 3 x 10(11), or 3 x 10(12) DRP) intramuscularly, either at a 6- or 12-month interval; follow-up was 18 months. Overall, 65% and 57% of vaccine recipients experienced local and systemic signs and symptoms, respectively, most being mild. Frequency and severity were not dose related and were similar to those in placebo recipients. No vaccine-related serious adverse events were reported. Overall, HIV-specific T cell responses were detected by IFN-gamma ELISPOT in 17/69 (25%) vaccine recipients with 38% (10/26) responders in the highest dosage group. The response rate improved significantly with boosting at 6, but not 12 months, in the 3 x 10(11) and 3 x 10(12) dosage groups only. Neutralizing antibody titers to the AAV2 did not alter the frequency of immune responses to HIV. Two doses of tgAAC09 were well tolerated at the dosage levels given. Fewer than half the recipients of the highest vaccine dosage, 3 x 10(12) DRP, had T cell responses to HIV.
authors.affiliation: Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, Soweto, South Africa.
authors.forename: Eftyhia
authors.initials: E
authors.lastname: Vardas
authors.forename: Pontiano
authors.initials: P
authors.lastname: Kaleebu
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.forename: Anwar
authors.initials: A
authors.lastname: Hoosen
authors.forename: Elwyn
authors.initials: E
authors.lastname: Chomba
authors.forename: Philip R
authors.initials: PR
authors.lastname: Johnson
authors.forename: Pervin
authors.initials: P
authors.lastname: Anklesaria
authors.forename: Josephine
authors.initials: J
authors.lastname: Birungi
authors.forename: Burc
authors.initials: B
authors.lastname: Barin
authors.forename: Mark
authors.initials: M
authors.lastname: Boaz
authors.forename: Josephine
authors.initials: J
authors.lastname: Cox
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lehrman
authors.forename: Gwynn
authors.initials: G
authors.lastname: Stevens
authors.forename: Jill
authors.initials: J
authors.lastname: Gilmour
authors.forename: Tony
authors.initials: T
authors.lastname: Tarragona
authors.forename: Peter
authors.initials: P
authors.lastname: Hayes
authors.forename: Sarah
authors.initials: S
authors.lastname: Lowenbein
authors.forename: Eva
authors.initials: E
authors.lastname: Kizito
authors.forename: Patricia
authors.initials: P
authors.lastname: Fast
authors.forename: Alison E
authors.initials: AE
authors.lastname: Heald
authors.forename: Claudia
authors.initials: C
authors.lastname: Schmidt
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000917:Antibody Formation; D000229:Dependovirus / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D005822:Genetic Vectors / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D014614:Vaccines, Synthetic