title: Delayed-type hypersensitivity responses to HIV Gag p24 relate to clinical outcome after peptide-based therapeutic immunization for chronic HIV infection.
abstract: Therapeutic immunization in chronic HIV infection aims to induce durable, HIV-specific immune responses capable of controlling disease progression, but immunological correlates of clinical efficacy are poorly defined. We have previously immunized 38 patients with a mixture of four short Gag p24-like conserved peptides (Vacc-4x) targeting skin dendritic cells. Antiretroviral treatment (ART) was initially stopped after completed immunizations and resumed post-protocol during regular clinical follow-up according to current guidelines. Four years after enrolment, Vacc-4x-specific cellular responses were evaluated in vivo by delayed-type hypersensitivity (DTH) skin test, and in vitro by a T-cell proliferation assay. Kaplan-Meier product-limit estimates were used to analyse time until ART was resumed. Peptide-specific cellular immune responses induced by Vacc-4x had persisted 4 years after the last immunization in terms of unchanged DTH independent of ART and detectable proliferative T-cell responses which correlated to the native peptides (R = 0.73, p = 0.01). Circulating bifunctional (IFN-γ and IL-10) Vacc-4x-specific T-cell clones were detected in 43% of patients. Subjects with the strongest post-immunization DTH responses appeared to start ART later compared with DTH low responders (p = 0.07). These data suggest that DTH responses should be further evaluated as a new and convenient tool for predicting clinical efficacy in trials testing therapeutic immunizations.
authors.affiliation: Department of Infectious Diseases, Oslo University Hospital, Norway. a.m.b.kran@medisin.uio.no
authors.forename: Anne-Marte B
authors.initials: AM
authors.lastname: Kran
authors.forename: Maja A
authors.initials: MA
authors.lastname: Sommerfelt
authors.forename: Ingebjørg
authors.initials: I
authors.lastname: Baksaas
authors.forename: Birger
authors.initials: B
authors.lastname: Sørensen
authors.forename: Dag
authors.initials: D
authors.lastname: Kvale
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D005500:Follow-Up Studies; D016655:HIV Core Protein p24 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D053208:Kaplan-Meier Estimate; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood
chemical_list: D016915:AIDS Vaccines; D016655:HIV Core Protein p24; D012367:RNA, Viral; C494182:Vacc-4x; D016753:Interleukin-10; D007371:Interferon-gamma