A phase 1/2 study of a multiclade HIV-1 DNA plasmid prime and recombinant adenovirus serotype 5 boost vaccine in HIV-Uninfected East Africans (RV 172)
Hannah Kibuuka, Robert Kimutai, Leonard Maboko, Fred Sawe, Mirjam S Schunk, Arne Kroidl, Douglas Shaffer, Leigh Anne Eller, Rukia Kibaya, Michael A Eller, Karin B Schindler, Alexandra Schuetz, Monica Millard, Jason Kroll, Len Dally, Michael Hoelscher, Robert Bailer, Josephine H Cox, Mary Marovich, Deborah L Birx, Barney S Graham, Nelson L Michael, Mark S de Souza, Merlin L Robb, Hannah Kibuuka, Robert Kimutai, Leonard Maboko, Fred Sawe, Mirjam S Schunk, Arne Kroidl, Douglas Shaffer, Leigh Anne Eller, Rukia Kibaya, Michael A Eller, Karin B Schindler, Alexandra Schuetz, Monica Millard, Jason Kroll, Len Dally, Michael Hoelscher, Robert Bailer, Josephine H Cox, Mary Marovich, Deborah L Birx, Barney S Graham, Nelson L Michael, Mark S de Souza, Merlin L Robb
Abstract
Background: Human immunodeficiency virus (HIV) vaccine development remains a global priority. We describe the safety and immunogenicity of a multiclade DNA vaccine prime with a replication-defective recombinant adenovirus serotype 5 (rAd5) boost.
Methods: The vaccine is a 6-plasmid mixture encoding HIV envelope (env) subtypes A, B, and C and subtype B gag, pol, and nef, and an rAd5 expressing identical genes, with the exception of nef. Three hundred and twenty-four participants were randomized to receive placebo (n=138), a single dose of rAd5 at 10(10) (n = 24) or 10(11) particle units (n = 24), or DNA at 0, 1, and 2 months, followed by rAd5 at either 10(10) (n= 114) or 10(11) particle units (n = 24) boosting at 6 months. Participants were followed up for 24 weeks after the final vaccination.
Results: The vaccine was safe and well tolerated. HIV-specific T cell responses were detected in 63% of vaccinees. Titers of preexisting Ad5 neutralizing antibody did not affect the frequency and magnitude of T cell responses in prime-boost recipients but did affect the response rates in participants that received rAd5 alone (P = .037).
Conclusion: The DNA/rAd5 vaccination regimen was safe and induced HIV type 1 multi-clade T cell responses, which were not significantly affected by titers of preexisting rAd5 neutralizing antibody. Trial Registration. ClinicalTrials.gov identifier: NCT00123968 .
Conflict of interest statement
The authors do not have a commercial or other association that might pose a conflict of interest.
Figures
Source: PubMed