Strain-specific protective immunity following vaccination against experimentalTrypanosoma cruziinfection

• Published in: Vaccine 2009-09, Vol.27 (41), p.5644
• Main Authors: Haolla, Filipe A, Claser, Carla, de Alencar, Bruna CG, Tzelepis, Fanny, de Vasconcelos, José Ronnie, de Oliveira, Gabriel, Silvério, Jaline C, Machado, Alexandre V, Lannes-Vieira, Joseli, Bruna-Romero, Oscar, Gazzinelli, Ricardo T, dos Santos, Ricardo Ribeiro, Soares, Milena BP, Rodrigues, Mauricio M
• Format: Article
• Language: English
• Subjects: Immunization; Parasites; Plasmids; Protozoa; Vaccines
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2009.07.013

Immunisation with Amastigote Surface Protein 2 (asp-2) andtrans-sialidase (ts) genes induces protective immunity in highly susceptible A/Sn mice, against infection with parasites of the Y strain ofTrypanosoma cruzi. Based on immunological and biological strain variations inT. cruziparasites, 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-2Kk-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 bothT. cruzigenes (asp-2andts) 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 againstT. cruziantigens, similar to viruses and bacteria, may be strain-specific and have a negative impact on vaccine development.