HIV-DNA Priming Alters T Cell Responses to HIV-Adenovirus Vaccine Even When Responses to DNA Are Undetectable.

Publication Type:

Journal Article

Source:

Journal of immunology (Baltimore, Md. : 1950), Volume 187, Issue 6, p.3391-3401 (2011)

Keywords:

2011, Adenoviridae, Adolescent, Adult, AIDS Vaccines, Antibodies, Viral', Cell Separation,, Center-Authored Paper, Enzyme-Linked Immunosorbent Assay, Female, Gene Products, env, Gene Products, gag, Gene Products, pol, HIV/immunology, Humans, Immunization, Secondary, Immunologic Memory/immunology Lymphocyte Activation, Male, Middle Aged, September 2011, T-Lymphocytes, Vaccination, Vaccine and Infectious Disease Division, Vaccines, DNA, Viral, Young Adult

Abstract:

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.