title: Strain-specific protective immunity following vaccination against experimental Trypanosoma cruzi infection.
abstract: Immunisation with Amastigote Surface Protein 2 (asp-2) and trans-sialidase (ts) genes induces protective immunity in highly susceptible A/Sn mice, against infection with parasites of the Y strain of Trypanosoma cruzi. Based on immunological and biological strain variations in T. cruzi parasites, our goal was to validate our vaccination results using different parasite strains. Due to the importance of the CD8(+) T cells in protective immunity, we initially determined which strains expressed the immunodominant H-2K(k)-restricted epitope TEWETGQI. We tested eight strains, four of which elicited immune responses to this epitope (Y, G, Colombian and Colombia). We selected the Colombian and Colombia strains for our studies. A/Sn mice were immunised with different regimens using both T. cruzi genes (asp-2 and ts) simultaneously and subsequently challenged with blood trypomastigotes. Immune responses before the challenge were confirmed by the presence of specific antibodies and peptide-specific T cells. Genetic vaccination did not confer protective immunity against acute infection with a lethal dose of the Colombian strain. In contrast, we observed a drastic reduction in parasitemia and a significant increase in survival, following challenge with an otherwise lethal dose of the Colombia strain. In many surviving animals with late-stage chronic infection, we observed alterations in the heart's electrical conductivity, compared to naive mice. In summary, we concluded that immunity against T. cruzi antigens, similar to viruses and bacteria, may be strain-specific and have a negative impact on vaccine development.
authors.affiliation: Centro Interdisciplinar de Terapia Gênica (CINTERGEN), Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, SP 04044-010, Brazil.
authors.forename: Filipe A
authors.initials: FA
authors.lastname: Haolla
authors.forename: Carla
authors.initials: C
authors.lastname: Claser
authors.forename: Bruna C G
authors.initials: BC
authors.lastname: de Alencar
authors.forename: Fanny
authors.initials: F
authors.lastname: Tzelepis
authors.forename: José Ronnie
authors.initials: JR
authors.lastname: de Vasconcelos
authors.forename: Gabriel
authors.initials: G
authors.lastname: de Oliveira
authors.forename: Jaline C
authors.initials: JC
authors.lastname: Silvério
authors.forename: Alexandre V
authors.initials: AV
authors.lastname: Machado
authors.forename: Joseli
authors.initials: J
authors.lastname: Lannes-Vieira
authors.forename: Oscar
authors.initials: O
authors.lastname: Bruna-Romero
authors.forename: Ricardo T
authors.initials: RT
authors.lastname: Gazzinelli
authors.forename: Ricardo Ribeiro
authors.initials: RR
authors.lastname: dos Santos
authors.forename: Milena B P
authors.initials: MB
authors.lastname: Soares
authors.forename: Mauricio M
authors.initials: MM
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D001483:Base Sequence; D014355:Chagas Disease / Q000517:prevention & control*; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000276:immunology*; D018512:Parasitemia / Q000517:prevention & control; D016052:Protozoan Vaccines / Q000276:immunology*; D016415:Sequence Alignment; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; C069715:trans-sialidase; C493236:ASP-2 protein, Trypanosoma cruzi; D009439:Neuraminidase