HIV-DNA priming alters T cell responses to HIV-adenovirus vaccine even when responses to DNA are undetectable.

TitleHIV-DNA priming alters T cell responses to HIV-adenovirus vaccine even when responses to DNA are undetectable.
Publication TypeJournal Article
Year of Publication2011
AuthorsDe Rosa SC, Thomas EP, Bui J, Huang Y, DeCamp AC, Morgan C, Kalams SA, Tomaras GD, Akondy R, Ahmed R, Lau C-Y, Graham BS, Nabel GJ, McElrath JM
Corporate AuthorsNational Institute of Allergy and Infectious Diseases HIV Vaccine Trials Network
JournalJ Immunol
Volume187
Issue6
Pagination3391-401
Date Published2011 Sep 15
ISSN1550-6606
KeywordsAdenoviridae, Adolescent, Adult, AIDS Vaccines, Antibodies, Viral, Cell Separation, DNA, Viral, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Gene Products, env, Gene Products, gag, Gene Products, pol, HIV, Humans, Immunization, Secondary, Immunologic Memory, Lymphocyte Activation, Male, Middle Aged, T-Lymphocytes, Vaccination, Vaccines, DNA, 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.

DOI10.4049/jimmunol.1101421
Alternate JournalJ. Immunol.
PubMed ID21844392