Safety and immunogenicity study of Multiclade HIV-1 adenoviral vector vaccine alone or as boost following a multiclade HIV-1 DNA vaccine in Africa
Walter Jaoko, Etienne Karita, Kayitesi Kayitenkore, Gloria Omosa-Manyonyi, Susan Allen, Soe Than, Elizabeth M Adams, Barney S Graham, Richard A Koup, Robert T Bailer, Carol Smith, Len Dally, Bashir Farah, Omu Anzala, Claude M Muvunyi, Jean Bizimana, Tony Tarragona-Fiol, Philip J Bergin, Peter Hayes, Martin Ho, Kelley Loughran, Wendy Komaroff, Gwynneth Stevens, Helen Thomson, Mark J Boaz, Josephine H Cox, Claudia Schmidt, Jill Gilmour, Gary J Nabel, Patricia Fast, Job Bwayo, Walter Jaoko, Etienne Karita, Kayitesi Kayitenkore, Gloria Omosa-Manyonyi, Susan Allen, Soe Than, Elizabeth M Adams, Barney S Graham, Richard A Koup, Robert T Bailer, Carol Smith, Len Dally, Bashir Farah, Omu Anzala, Claude M Muvunyi, Jean Bizimana, Tony Tarragona-Fiol, Philip J Bergin, Peter Hayes, Martin Ho, Kelley Loughran, Wendy Komaroff, Gwynneth Stevens, Helen Thomson, Mark J Boaz, Josephine H Cox, Claudia Schmidt, Jill Gilmour, Gary J Nabel, Patricia Fast, Job Bwayo
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 1×10(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.
Trial registration: ClinicalTrials.gov NCT00124007.
Conflict of interest statement
Competing Interests: IAVI is a non-profit organization. None of the co-authors affiliated with IAVI reports any competing interest, that might interfere with the objective assessment of this manuscript or with the ability to adhere to all PloS ONE policies on sharing data and materials. Gary J. Nabel is named on patent applications for the DNA and adenovirus vector components of this vaccine concept (patents # E-173-2004/0-US-01, E-355-2003/0-US-01, and E-267-2004/0). This does not alter the author's ability to adhere to all PloS ONE policies on sharing data and materials. None of the co-authors employed by government agencies declares any competing interest that might interfere with the objective assessment of this manuscript or with the ability to adhere to all PloS ONE policies on sharing data and materials. Affiliations of Carol Smith, Len Dally, Martin Ho, Kelley Loughran, Mark Boaz and Soe Than do not alter the authors' ability to adhere to all the PLoS ONE policies on sharing data and materials. Drs. Than and Boaz report no competing interests.
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Source: PubMed