| Author | Titus, Richard G | |
| Author | Gueiros Filho, Frederico J. | |
| Author | Freitas, Luiz Antonio Rodrigues de | |
| Author | Beverley, Stephen M | |
| Access date | 2014-07-10T13:11:53Z | |
| Available date | 2014-07-10T13:11:53Z | |
| Document date | 1995 | |
| 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. | pt_BR |
| ISSN | 0027-8424 | |
| URI | https://www.arca.fiocruz.br/handle/icict/7902 | |
| Language | eng | pt_BR |
| Publisher | American Society for Microbiology | pt_BR |
| Rights | open access | pt_BR |
| Title | Development of a safe live Leishmania vaccine line by gene replacement. | pt_BR |
| Type | Article | pt_BR |
| 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. | pt_BR |
| 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 | pt_BR |
| Affilliation | Harvard Medical School. Department of Biological Chemistry and Molecular Pharmacology. Boston, MA | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | Harvard Medical School. Department of Biological Chemistry and Molecular Pharmacology. Boston, MA | pt_BR |
| DeCS | Leishmania major/crescimento & desenvolvimento | pt_BR |
| DeCS | Leishmania major/imunologia | pt_BR |
| DeCS | Leishmaniose Cutânea/imunologia | pt_BR |
| DeCS | Vacinas Protozoárias/imunologia | pt_BR |
| DeCS | Vacinas Atenuadas/imunologia | pt_BR |
| DeCS | Animais | pt_BR |
| DeCS | Marcação de Genes | pt_BR |
| DeCS | Humanos | pt_BR |
| DeCS | Leishmaniose Cutânea/prevenção & controle | pt_BR |
| DeCS | Macrófagos/parasitologia | pt_BR |
| DeCS | Camundongos | pt_BR |
| DeCS | Camundongos Endogâmicos BALB C | pt_BR |
| DeCS | Camundongos Nus | pt_BR |
| DeCS | Especificidade da Espécie | pt_BR |
| DeCS | Timidina/farmacologia | pt_BR |
| DeCS | Fatores de Tempo | pt_BR |
