Strain-specific protective immunity following vaccination against experimental Trypanosoma cruzi infection.
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.
Haolla
Filipe A
FA
Centro Interdisciplinar de Terapia Gênica (CINTERGEN), Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, SP 04044-010, Brazil.
Claser
Carla
C
de Alencar
Bruna C G
BC
Tzelepis
Fanny
F
de Vasconcelos
José Ronnie
JR
de Oliveira
Gabriel
G
Silvério
Jaline C
JC
Machado
Alexandre V
AV
Lannes-Vieira
Joseli
J
Bruna-Romero
Oscar
O
Gazzinelli
Ricardo T
RT
dos Santos
Ricardo Ribeiro
RR
Soares
Milena B P
MB
Rodrigues
Mauricio M
MM
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*
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