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

Mem Inst Oswaldo Cruz. Jul-Aug 1999;94(4):491-6. doi: 10.1590/s0074-02761999000400011.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Protozoan / administration & dosage*
  • Leishmania major / immunology*
  • Leishmaniasis, Cutaneous / immunology
  • Leishmaniasis, Cutaneous / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, Mutant Strains
  • Multienzyme Complexes / immunology*
  • Protozoan Vaccines / immunology*
  • Tetrahydrofolate Dehydrogenase / immunology*
  • Thymidylate Synthase / immunology*

Substances

  • Antigens, Protozoan
  • Multienzyme Complexes
  • Protozoan Vaccines
  • thymidylate synthase-dihydrofolate reductase
  • Tetrahydrofolate Dehydrogenase
  • Thymidylate Synthase