Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/7902
Title: Development of a safe live Leishmania vaccine line by gene replacement.
Authors: Titus, Richard G
Gueiros Filho, Frederico J.
Freitas, Luiz Antonio Rodrigues de
Beverley, Stephen M
Affilliation: Colorado State University. Department of Pathology. College of Veterinary Medicine and Biomedical Sciences. Fort Collins, USA / Harvard School of Public Health. Department of Tropical Public Health. Boston, MA
Harvard Medical School. Department of Biological Chemistry and Molecular Pharmacology. Boston, MA
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Harvard Medical School. Department of Biological Chemistry and Molecular Pharmacology. Boston, MA
Abstract: Vaccination 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.
DeCS: Leishmania major/crescimento & desenvolvimento
Leishmania major/imunologia
Leishmaniose Cutânea/imunologia
Vacinas Protozoárias/imunologia
Vacinas Atenuadas/imunologia
Animais
Marcação de Genes
Humanos
Leishmaniose Cutânea/prevenção & controle
Macrófagos/parasitologia
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Especificidade da Espécie
Timidina/farmacologia
Fatores de Tempo
Issue Date: 1995
Publisher: American Society for Microbiology
Citation: TITUS, 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.
ISSN: 0027-8424
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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