title: Qualitative T-helper responses to multiple viral antigens correlate with vaccine-induced immunity to simian/human immunodeficiency virus infection.
abstract: Evidence is accumulating that CD4(+) T-helper (Th) responses play a critical role in facilitating effector responses which are capable of controlling and even preventing human immunodeficiency virus (HIV) infection. The present work was undertaken to determine whether immunization with multiple antigens influenced individual Th responses and increased protection relative to a single antigen. Rhesus macaques were primed with DNA and boosted (immune-stimulating complex-formulated protein) with a combination of regulatory and structural antigens (Tat-Env-Gag) or with Tat alone. Immunization with combined antigens reduced the magnitude of the responses to Tat compared to the single-antigen immunization. Interestingly, the Th immune responses to the individual antigens were noticeably different. To determine whether the qualitative differences in vaccine-induced Th responses correlated with vaccine efficacy, animals were challenged intravenously with simian/human immunodeficiency virus (strain SHIV(89.6p)) 2 months following the final immunization. Animals that developed combined Th1- and Th2-like responses to Gag and Th2 dominant Env-specific responses were protected from disease progression. Interestingly, one animal that was completely protected from infection had the strongest IFN-gamma and interleukin-2 (IL-2) responses prior to challenge, in addition to very strong IL-4 responses to Gag and Env. In contrast, animals with only a marked vaccine-induced Tat-specific Th2 response (no IFN-gamma) were not protected from infection or disease. These data support the rationale that effective HIV vaccine-induced immunity requires a combination of potent Th1- and Th2-like responses best directed to multiple antigens.
authors.affiliation: Department of Virology, Biomedical Primate Research Center, 2280 GH Rijswijk, The Netherlands. mooij@bprc.nl
authors.forename: Petra
authors.initials: P
authors.lastname: Mooij
authors.forename: Ivonne G
authors.initials: IG
authors.lastname: Nieuwenhuis
authors.forename: Christiaan J
authors.initials: CJ
authors.lastname: Knoop
authors.forename: Robert W
authors.initials: RW
authors.lastname: Doms
authors.forename: Willy M J M
authors.initials: WM
authors.lastname: Bogers
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Ten Haaft
authors.forename: Henk
authors.initials: H
authors.lastname: Niphuis
authors.forename: Wim
authors.initials: W
authors.lastname: Koornstra
authors.forename: Kurt
authors.initials: K
authors.lastname: Bieler
authors.forename: Josef
authors.initials: J
authors.lastname: Köstler
authors.forename: Brør
authors.initials: B
authors.lastname: Morein
authors.forename: Aurelio
authors.initials: A
authors.lastname: Cafaro
authors.forename: Barbara
authors.initials: B
authors.lastname: Ensoli
authors.forename: Ralf
authors.initials: R
authors.lastname: Wagner
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Heeney
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019562:Viral Load
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D015488:HIV Antigens; D012367:RNA, Viral; D018449:SAIDS Vaccines