Development of a safe live Leishmania vaccine line by gene replacement.

dc.creatorTitus, Richard G
dc.creatorGueiros Filho, Frederico J.
dc.creatorFreitas, Luiz Antonio Rodrigues de
dc.creatorBeverley, Stephen M
dc.date2014-07-10T13:11:53Z
dc.date2014-07-10T13:11:53Z
dc.date1995
dc.date.accessioned2023-09-26T21:15:07Z
dc.date.available2023-09-26T21:15:07Z
dc.identifierTITUS, R. G. et al. Development of a safe live Leishmania vaccine line by gene replacement. Proceedings of the National Academy Science of the USA, v. 92, n. 22, p. 10267-10271, 1995.
dc.identifier0027-8424
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/7902
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8871525
dc.descriptionVaccination with live Leishmania major has been shown to yield effective immunization in humans; however, this has been discontinued because of problems associated with virulence of the available vaccine lines. To circumvent this, we tested the ability of a dhfr-ts- null mutant of L. major, obtained by gene targeting, to infect and then to vaccinate mice against challenge with virulent L. major. Survival and replication of dhfr-ts- in macrophages in vitro were dependent upon thymidine, with parasites differentiating into amastigotes prior to destruction. dhfr-ts- parasites persisted in BALB/c mice for up to 2 months, declining with a half-life of 2-3 days. Nonetheless, dhfr-ts- was incapable of causing disease in both susceptible and immunodeficient (nu/nu) BALB/c mice. Animal infectivity could be partially restored by thymidine supplementation. When inoculated by the i.v., s.c., or i.m. routes into mice, dhfr-ts- could elicit substantial resistance to a subsequent challenge with virulent L. major. Thus, Leishmania bearing auxotrophic gene knockouts can be safe and induce protective immunity. Potentially, dhfr-ts- could be used as a platform for delivery of immunogens relevant to other diseases.
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Society for Microbiology
dc.rightsopen access
dc.subjectLeishmania major/crescimento & desenvolvimento
dc.subjectLeishmania major/imunologia
dc.subjectLeishmaniose Cutânea/imunologia
dc.subjectVacinas Protozoárias/imunologia
dc.subjectVacinas Atenuadas/imunologia
dc.subjectAnimais
dc.subjectMarcação de Genes
dc.subjectHumanos
dc.subjectLeishmaniose Cutânea/prevenção & controle
dc.subjectMacrófagos/parasitologia
dc.subjectCamundongos
dc.subjectCamundongos Endogâmicos BALB C
dc.subjectCamundongos Nus
dc.subjectEspecificidade da Espécie
dc.subjectTimidina/farmacologia
dc.subjectFatores de Tempo
dc.titleDevelopment of a safe live Leishmania vaccine line by gene replacement.
dc.typeArticle


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