TY - JOUR
T1 - Safety and immunogenicity study of multiclade HIV-1 adenoviral vector vaccine alone or as boost following a multiclade HIV-1 DNA vaccine in Africa
AU - Jaoko, Walter
AU - Karita, Etienne
AU - Kayitenkore, Kayitesi
AU - Omosa-Manyonyi, Gloria
AU - Allen, Susan
AU - Than, Soe
AU - Adams, Elizabeth M.
AU - Graham, Barney S.
AU - Koup, Richard A.
AU - Bailer, Robert T.
AU - Smith, Carol
AU - Dally, Len
AU - Farah, Bashir
AU - Anzala, Omu
AU - Muvunyi, Claude M.
AU - Bizimana, Jean
AU - Tarragona-Fiol, Tony
AU - Bergin, Philip J.
AU - Ho, Peter Hayes Martin
AU - Loughran, Kelley
AU - Komaroff, Wendy
AU - Stevens, Gwynneth
AU - Thomson, Helen
AU - Boaz, Mark J.
AU - Cox, Josephine H.
AU - Schmidt, Claudia
AU - Gilmour, Jill
AU - Nabel, Gary J.
AU - Fast, Patricia
AU - Bwayo, Job
PY - 2010
Y1 - 2010
N2 - Background: We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replicationdefective 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 HIVuninfected 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-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 welltolerated 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.
AB - Background: We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replicationdefective 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 HIVuninfected 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-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 welltolerated 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.
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U2 - 10.1371/journal.pone.0012873
DO - 10.1371/journal.pone.0012873
M3 - Article
C2 - 20877623
AN - SCOPUS:77958498605
SN - 1932-6203
VL - 5
SP - 1
EP - 16
JO - PLoS One
JF - PLoS One
IS - 9
M1 - e12873
ER -