HIV-DNA priming alters T cell responses to HIV-adenovirus vaccine even when responses to DNA are undetectable.
Many candidate HIV vaccines are designed to primarily elicit T cell responses. Although repeated immunization with the same vaccine boosts Ab responses, the benefit for T cell responses is ill defined. We compared two immunization regimens that include the same recombinant adenoviral serotype 5 (rAd5) boost. Repeated homologous rAd5 immunization fails to increase T cell responses, but increases gp140 Ab responses 10-fold. DNA prime, as compared with rAd5 prime, directs long-term memory CD8(+) T cells toward a terminally differentiated effector memory phenotype with cytotoxic potential. Based on the kinetics of activated cells measured directly ex vivo, the DNA vaccination primes for both CD4(+) and CD8(+) T cells, despite the lack of detection of the latter until after the boost. These results suggest that heterologous prime-boost combinations have distinct immunological advantages over homologous prime-boosts and suggest that the effect of DNA on subsequent boosting may not be easily detectable directly after the DNA vaccination.
De Rosa, SC; Thomas, EP; Bui, J; Huang, Y; deCamp, A; Morgan, C; Kalams, SA; Tomaras, GD; Akondy, R; Ahmed, R; Lau, C-Y; Graham, BS; Nabel, GJ; McElrath, MJ; National Institute of Allergy and Infectious Diseases HIV Vaccine Trials Network,
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