title: 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.
authors.affiliation: Laboratório de Patologia e Biologia Celular, Fiocruz, Salvador, BA, 40295-001, Brasil. pveras@svn.com.br
authors.forename: P
authors.initials: P
authors.lastname: Veras
authors.forename: C
authors.initials: C
authors.lastname: Brodskyn
authors.forename: F
authors.initials: F
authors.lastname: Balestieri
authors.forename: L d
authors.initials: Ld
authors.lastname: Freitas
authors.forename: A
authors.initials: A
authors.lastname: Ramos
authors.forename: A
authors.initials: A
authors.lastname: Queiroz
authors.forename: A
authors.initials: A
authors.lastname: Barral
authors.forename: S
authors.initials: S
authors.lastname: Beverley
authors.forename: M
authors.initials: M
authors.lastname: Barral-Netto
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009097:Multienzyme Complexes / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology*; D013762:Tetrahydrofolate Dehydrogenase / Q000276:immunology*; D013940:Thymidylate Synthase / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D009097:Multienzyme Complexes; D016052:Protozoan Vaccines; C056930:thymidylate synthase-dihydrofolate reductase; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase