Safety and Immunogenicity Study of Multiclade HIV-1 Adeno-Viral Vector Vaccine Alone or as Boost Following a Multiclade HIV-1 DNA Vaccine in Africa
09/2010
Journal Article
Authors:
Jaoko, W.;
Karita, E.;
Kayitenkore, K.;
Omosa-Manyonyi, G.;
Allen, S.;
Than, S.;
Adams, E.;
Graham, B.;
Koup, R.;
Bailer, R.;
Smith, C.;
Dally, L.;
Farah, B.;
Anzala, O.;
Muvunyi, C.;
Bizimana, J.;
Tarragona-Fiol, T.;
Bergin, P.;
Hayes, P.;
Ho, M.;
Loughran, K.;
Komaroff, W.
Secondary:
PLoS ONE
Volume:
5
Pagination:
e12873
URL:
http://www.ncbi.nlm.nih.gov/pubmed/20877623
Keywords:
Antibodies-Viral/immunology; Double-Blind; Drug Toxicity; Genetic Vectors/adverse effects/genetics/immunology; HIV Infections/immunology/prevention & control/virology; HIV-1/classification/genetics/immunology; Humans; Immunization-Secondary; Male
Abstract:
Background: We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replication-defective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIV-uninfected African adults. Methodology/Principal Findings: Volunteers were randomized to 4 groups receiving the rAd5 vaccine intramuscularly at dosage levels of 1×1010 or 1×1011 particle units (PU) either alone or as boost following 3 injections of the DNA vaccine given at 4 mg/dose intramuscularly by needle-free injection using Biojector® 2000. Safety and immunogenicity were evaluated for 12 months. Both vaccines were well-tolerated. Overall, 62% and 86% of vaccine recipients in the rAd5 alone and DNA prime - rAd5 boost groups, respectively, responded to the HIV-1 proteins by an interferon-gamma (IFN-?) ELISPOT. The frequency of immune responses was independent of rAd5 dosage levels. The highest frequency of responses after rAd5 alone was detected at 6 weeks; after DNA prime - rAd5 boost, at 6 months (end of study). At baseline, neutralizing antibodies against Ad5 were present in 81% of volunteers; the distribution was similar across the 4 groups. Pre-existing immunity to Ad5 did not appear to have a significant impact on reactogenicity or immune response rates to HIV antigens by IFN-? ELISPOT. Binding antibodies against Env were detected in up to 100% recipients of DNA prime - rAd5 boost. One volunteer acquired HIV infection after the study ended, two years after receipt of rAd5 alone. Conclusions/Significance: The HIV-1 rAd5 vaccine, either alone or as a boost following HIV-1 DNA vaccine, was well-tolerated and immunogenic in African adults. DNA priming increased the frequency and magnitude of cellular and humoral immune responses, but there was no effect of rAd5 dosage on immunogenicity endpoints.
