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A dhfr-ts- Leishmania major knockout mutant cross-protects against Leishmania amazonensis.

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.
AuthorsP Veras, C Brodskyn, F Balestieri, L d Freitas, A Ramos, A Queiroz, A Barral, S Beverley, M Barral-Netto
JournalMemorias do Instituto Oswaldo Cruz (Mem Inst Oswaldo Cruz) 1999 Jul-Aug Vol. 94 Issue 4 Pg. 491-6 ISSN: 0074-0276 [Print] Brazil
PMID10446007 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, Protozoan
  • Multienzyme Complexes
  • Protozoan Vaccines
  • thymidylate synthase-dihydrofolate reductase
  • Tetrahydrofolate Dehydrogenase
  • Thymidylate Synthase
Topics
  • Animals
  • Antigens, Protozoan (administration & dosage)
  • Leishmania major (immunology)
  • Leishmaniasis, Cutaneous (immunology, prevention & control)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, Mutant Strains
  • Multienzyme Complexes (immunology)
  • Protozoan Vaccines (immunology)
  • Tetrahydrofolate Dehydrogenase (immunology)
  • Thymidylate Synthase (immunology)

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