DNA sequences encoding CD4+ and CD8+T-cell epitopes are important for efficient protective immunity induced by DNA vaccination with a Trypanosoma cruzi gene

DNA sequences encoding CD4+ and CD8+T-cell epitopes are important for efficient protective immunity induced by DNA vaccination with a Trypanosoma cruzi gene

Autor Fujimura, Adriana E. Autor UNIFESP Google Scholar
Kinoshita, Sheila S. Autor UNIFESP Google Scholar
Pereira-Chioccola, Vera L. Google Scholar
Rodrigues, Mauricio M. Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Inst Adolfo Lutz Registro
Resumo Immunization of BALB/c mice with a plasmid containing the gene for Trypanosoma cruzi trans-sialidase (TS) induced antibodies that inhibited TS enzymatic activity, CD4(+) Th1 and CD8(+) Tc1 cells, and protective immunity against infection. We used this model to obtain basic information on the requirement of CD4 or CD8 or B-cell epitopes for an effective DNA-induced immunity against T. cruzi infection. for that purpose, mice were immunized with plasmids containing DNA sequences encoding (i) the entire TS protein, (ii) the TS enzymatic domain, (iii) the TS CD4(+) T-cell epitopes, (iv) the TS CD8(+) T-cell epitope, or (v) TS CD4(+) and CD8(+) T-cell epitopes. Plasmids expressing the entire TS or its enzymatic domain elicited similar levels of TS-inhibitory antibodies, gamma interferon (IFN-gamma) -producing T cells, and protective immunity against infection. Although the plasmid expressing TS CD4 epitopes was immunogenic, its protective efficacy against experimental infection was limited. the plasmid expressing the CD8 epitope was poorly immunogenic and provided little protective immunity. the reason for the limited priming of CD8(+) T cells was due to a requirement for CD4(+) T cells. To circumvent this problem, a plasmid expressing both CD4(+) and CD8(+) T-cell epitopes was produced. This plasmid generated levels of IFN-gamma -producing T cells and protective: immunity comparable to that of the plasmid expressing the entire catalytic domain of TS. Our observations suggest that plasmids expressing epitopes recognized by CD4(+) and CD8(+) T cells may have a better protective potential against infection with T. cruzi.
Idioma Inglês
Data de publicação 2001-09-01
Publicado em Infection and Immunity. Washington: Amer Soc Microbiology, v. 69, n. 9, p. 5477-5486, 2001.
ISSN 0019-9567 (Sherpa/Romeo, fator de impacto)
Publicador Amer Soc Microbiology
Extensão 5477-5486
Fonte http://dx.doi.org/10.1128/IAI.69.9.5477-5486.2001
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000170540000033
Endereço permanente http://repositorio.unifesp.br/handle/11600/26615

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