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)

作者：Kibuuka Hannah; Kimutai Robert; Maboko Leonard; Sawe Fred; Schunk Mirjam S; Kroidl Arne; Shaffer Douglas; Eller Leigh Anne; Kibaya Rukia; Eller Michael A; Schindler Karin B; Schuetz Alexandra; Millard Monica; Kroll Jason; Dally Len; Hoelscher Michael; Bailer Robert; Cox Josephine H; Marovich Mary; Birx Deborah L; Graham Barney S; Michael Nelson L; de Souza Mark S; Robb Merlin L^*

来源：Journal of Infectious Diseases, 2010, 201(4): 600-607.

DOI：10.1086/650299

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.

• 出版日期2010-2-15
• 单位河北医科大学