A dhfr-ts- Leishmania major Knockout Mutant Cross-protects against Leishmania amazonensis

P. S.T. Veras, C. I. Brodskyn, F. M.P. Balestieri, L. A.R. De Freitas, A. P.S. Ramos, A. R.P. Queiroz, A. Barral, S. M. Beverley, M. Barral-Netto

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44 Scopus citations

Abstract

E10-5A3 is a dhfr-ts- Leishmania major double knockout auxotrophic shown previously to induce substantial protection against virulent L. major infection in both genetically susceptible and resistant mice. We investigated the capacity of dhfr-ts- to protect against heterologous infection by L. amazonensis. The degree of protection was evaluated by immunization of BALB/c or C57BL/6 mice with E10-5A3, followed by L. amazonensis challenge. Whether immunized by subcutaneous (SC) or intravenous (IV) inoculation, susceptible and resistant mice displayed a partial degree of protection against challenge with virulent L. amazonensis. SC-immunized BALB/c mice developed lesions 40 to 65% smaller than non immunized mice, while IV immunization led to protection ranging from 40 to 75% in four out of six experiments compared to non immunized animals. The resistant C57BL/6 mice displayed comparable degrees of protection, 57% by SC and 49% by IV immunization. Results are encouraging as it has been previously difficult to obtain protection by SC vaccination against Leishmania, the preferred route for human immunization.

Original languageEnglish
Pages (from-to)491-496
Number of pages6
JournalMemorias do Instituto Oswaldo Cruz
Volume94
Issue number4
DOIs
StatePublished - 1999

Keywords

  • Auxotrophic Leishmania major
  • Cross-protection
  • Immunization
  • Leishmania amazonensis

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