title: Trypanosoma cruzi adjuvants potentiate T cell-mediated immunity induced by a NY-ESO-1 based antitumor vaccine.
abstract: Immunological adjuvants that induce T cell-mediate immunity (TCMI) with the least side effects are needed for the development of human vaccines. Glycoinositolphospholipids (GIPL) and CpGs oligodeoxynucleotides (CpG ODNs) derived from the protozoa parasite Trypanosoma cruzi induce potent pro-inflammatory reaction through activation of Toll-Like Receptor (TLR)4 and TLR9, respectively. Here, using mouse models, we tested the T. cruzi derived TLR agonists as immunological adjuvants in an antitumor vaccine. For comparison, we used well-established TLR agonists, such as the bacterial derived monophosphoryl lipid A (MPL), lipopeptide (Pam3Cys), and CpG ODN. All tested TLR agonists were comparable to induce antibody responses, whereas significant differences were noticed in their ability to elicit CD4(+) T and CD8(+) T cell responses. In particular, both GIPLs (GTH, and GY) and CpG ODNs (B344, B297 and B128) derived from T. cruzi elicited interferon-gamma (IFN-γ) production by CD4(+) T cells. On the other hand, the parasite derived CpG ODNs, but not GIPLs, elicited a potent IFN-γ response by CD8(+) T lymphocytes. The side effects were also evaluated by local pain (hypernociception). The intensity of hypernociception induced by vaccination was alleviated by administration of an analgesic drug without affecting protective immunity. Finally, the level of protective immunity against the NY-ESO-1 expressing melanoma was associated with the magnitude of both CD4(+) T and CD8(+) T cell responses elicited by a specific immunological adjuvant.
authors.affiliation: Laboratório de Imunopatologia, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil.
authors.forename: Caroline
authors.initials: C
authors.lastname: Junqueira
authors.forename: Ana Tereza
authors.initials: AT
authors.lastname: Guerrero
authors.forename: Bruno
authors.initials: B
authors.lastname: Galvão-Filho
authors.forename: Warrison A
authors.initials: WA
authors.lastname: Andrade
authors.forename: Ana Paula C
authors.initials: AP
authors.lastname: Salgado
authors.forename: Thiago M
authors.initials: TM
authors.lastname: Cunha
authors.forename: Catherine
authors.initials: C
authors.lastname: Ropert
authors.forename: Marco Antônio
authors.initials: MA
authors.lastname: Campos
authors.forename: Marcus L O
authors.initials: ML
authors.lastname: Penido
authors.forename: Lúcia
authors.initials: L
authors.lastname: Mendonça-Previato
authors.forename: José Oswaldo
authors.initials: JO
authors.lastname: Previato
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.forename: Ricardo T
authors.initials: RT
authors.lastname: Gazzinelli
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D008545:Melanoma / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D008565:Membrane Proteins