A dhfr-ts- Leishmania major knockout mutant cross-protects against Leishmania amazonensis.
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.
Veras
P
P
Laboratório de Patologia e Biologia Celular, Fiocruz, Salvador, BA, 40295-001, Brasil. pveras@svn.com.br
Brodskyn
C
C
Balestieri
F
F
Freitas
L d
Ld
Ramos
A
A
Queiroz
A
A
Barral
A
A
Beverley
S
S
Barral-Netto
M
M
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*
D000953:Antigens, Protozoan; D009097:Multienzyme Complexes; D016052:Protozoan Vaccines; C056930:thymidylate synthase-dihydrofolate reductase; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase