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Strain-specific protective immunity following vaccination against experimental Trypanosoma cruzi infection.

By Filipe Augusto Bettencourt Haolla, Carla Clasera, Bruna Cunha de Alencar Bargieri, Fanny Tzelepisa, José Ronnie Carvalho de Vasconcelos, Gabriel Melo de Oliveira, Jaline Coutinho Silvério, Alexandre Vieira Machado, Joseli Lannes Vieira, Oscar Bruna-Romero, Ricardo Tostes Gazzinelli, Ricardo Ribeiro dos Santos, Milena Botelho Pereira Soares and Maurício Martins Rodrigues

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

Topics: Trypanosoma cruzi, DNA vaccine, Adenovirus vaccine, CD8, Doença de Chagas/prevenção & controle, Glicoproteínas/imunologia, Neuraminidase/imunologia, Vacinas Protozoárias/imunologia, Trypanosoma cruzi/imunologia, Vacinas de DNA/imunologia, Anticorpos Antiprotozoários/sangue, Animais, Sequência de Bases, Reações Cruzadas, Epitopos de Linfócito T/imunologia, Feminino, Humanos, Camundongos, Dados de Sequência Molecular, Parasitemia/prevenção & controle, Alinhamento de Sequência, Análise de Sobrevida, Linfócitos T/imunologia
Publisher: Elsevier
Year: 2009
OAI identifier: oai:agregador.ibict.br.RI_FIOCRUZ:oai:localhost:icict/9019
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