Safety and immunogenicity study of Multiclade HIV-1 adenoviral vector vaccine alone or as boost following a multiclade HIV-1 DNA vaccine in Africa.

Publication Type
Journal Article
Year of Publication
Jaoko, Walter; Karita, Etienne; Kayitenkore, Kayitesi; Omosa-Manyonyi, Gloria; Allen, Susan; Than, Soe; Adams, Elizabeth M; Graham, Barney S; Koup, Richard A; Bailer, Robert T; Smith, Carol; Dally, Len; Farah, Bashir; Anzala, Omu; Muvunyi, Claude M; Bizimana, Jean; Tarragona-Fiol, Tony; Bergin, Philip J; Hayes, Peter; Ho, Martin; Loughran, Kelley; Komaroff, Wendy; Stevens, Gwynneth; Thomson, Helen; Boaz, Mark J; Cox, Josephine H; Schmidt, Claudia; Gilmour, Jill; Nabel, Gary J; Fast, Patricia; Bwayo, Job
PLoS One
Date Published
2010 Sep 21
Adenoviridae; Adolescent; Adult; AIDS Vaccines; Antibodies, Viral; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; gag Gene Products, Human Immunodeficiency Virus; Genetic Vectors; HIV Infections; HIV-1; Humans; Immunization, Secondary; Male; Middle Aged; pol Gene Products, Human Immunodeficiency Virus; Vaccines, DNA; Young Adult

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 1×10(10) or 1×10(11) 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-γ) 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-γ 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.