title: Magnitude and phenotype of cellular immune responses elicited by recombinant adenovirus vectors and heterologous prime-boost regimens in rhesus monkeys.
abstract: Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for human immunodeficiency virus type 1 (HIV-1) and other pathogens have been shown to elicit antigen-specific cellular immune responses. Rare serotype rAd vectors have also been constructed to circumvent preexisting anti-Ad5 immunity and to facilitate the development of novel heterologous rAd prime-boost regimens. Here we show that rAd5, rAd26, and rAd48 vectors elicit qualitatively distinct phenotypes of cellular immune responses in rhesus monkeys and can be combined as potent heterologous prime-boost vaccine regimens. While rAd5-Gag induced primarily gamma interferon-positive (IFN-gamma(+)) and IFN-gamma(+)/tumor necrosis factor alpha(+) (TNF-alpha(+)) T-lymphocyte responses, rAd26-Gag and rAd48-Gag induced higher proportions of interleukin-2(+) (IL-2(+)) and polyfunctional IFN-gamma(+)/TNF-alpha(+)/IL-2(+) T-lymphocyte responses. Priming with the rare serotype rAd vectors proved remarkably effective for subsequent boosting with rAd5 vectors. These data demonstrate that the rare serotype rAd vectors elicited T-lymphocyte responses that were phenotypically distinct from those elicited by rAd5 vectors and suggest the functional relevance of polyfunctional CD8(+) and CD4(+) T-lymphocyte responses. Moreover, qualitative differences in cellular immune responses may prove critical in determining the overall potency of heterologous rAd prime-boost regimens.
authors.affiliation: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Liu
authors.forename: Bonnie A
authors.initials: BA
authors.lastname: Ewald
authors.forename: Diana M
authors.initials: DM
authors.lastname: Lynch
authors.forename: Matthew
authors.initials: M
authors.lastname: Denholtz
authors.forename: Peter
authors.initials: P
authors.lastname: Abbink
authors.forename: Angelique A C
authors.initials: AA
authors.lastname: Lemckert
authors.forename: Angela
authors.initials: A
authors.lastname: Carville
authors.forename: Keith G
authors.initials: KG
authors.lastname: Mansfield
authors.forename: Menzo J
authors.initials: MJ
authors.lastname: Havenga
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007117:Immunization, Secondary / Q000379:methods; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D015683:Gene Products, gag; D007376:Interleukin-2; D018449:SAIDS Vaccines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma