title: HIV-DNA priming alters T cell responses to HIV-adenovirus vaccine even when responses to DNA are undetectable.
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.
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA. sderosa@fhcrc.org
authors.forename: Stephen C
authors.initials: SC
authors.lastname: De Rosa
authors.forename: Evan P
authors.initials: EP
authors.lastname: Thomas
authors.forename: John
authors.initials: J
authors.lastname: Bui
authors.forename: Yunda
authors.initials: Y
authors.lastname: Huang
authors.forename: Allan
authors.initials: A
authors.lastname: deCamp
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morgan
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Rama
authors.initials: R
authors.lastname: Akondy
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.forename: Chuen-Yen
authors.initials: CY
authors.lastname: Lau
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002469:Cell Separation; D004279:DNA, Viral / Q000008:administration & dosage / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015684:Gene Products, pol / Q000276:immunology; D006678:HIV / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods*; D007156:Immunologic Memory / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D004279:DNA, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D015684:Gene Products, pol; D019444:Vaccines, DNA