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 infec tion in both genetically susceptible and resistant mice. We investigated th e capacity of dhfr-ts(-) to protect against heterologous infection by L. am azonensis. The degree of protection was evaluated by immunization of BALB/c or C57BL/6 mice with E10-5A3, followed by L. amazonensis challenge. Whethe r immunized by subcutaneous (SC) or intravenous (IV) inoculation, susceptib le and resistant mice displayed a partial degree of protection against chal lenge with virulent L. amazonensis. SC-immunized BALB/c mice developed lesi ons 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 d egrees of protection, 57% by SC and 49% by IV immunization. Results are enc ouraging as it has been previously difficult to obtain protection by SC vac cination against Leishmania, the preferred route for human immunization.