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Development of a recombinant Leishmania major strain sensitive to ganciclovir and 5-fluorocytosine for use as a live vaccine challenge in clinical trials.

Abstract：

:To provide a safer live challenge strain for use in clinical vaccine trials, a double drug sensitive strain of Leishmania major was derived using advances in gene targeting technology by stably introducing into the chromosome a modified HSV-1 thymidine kinase gene (tk), conferring increased sensitivity to ganciclovir (GCV), and a Saccharomyces cerevisiae cytosine deaminase gene (cd), conferring sensitivity to 5-fluorocytosine (5-FC). In vitro studies showed that the homozygous L. major (tk-cd+/+) promastigotes were killed by either drug alone, and together the drugs acted synergistically. In vivo infection studies showed that progressively growing lesions in BALB/c mice, caused by L. major (tk-cd+/+), were completely cured by 2 weeks of treatment with either drug alone or in combination. Treated animals showed no signs of reoccurrence of infection for at least 4 months when the experiments were terminated.

journal_name

Vaccine

journal_title

Vaccine

authors

Davoudi N,Tate CA,Warburton C,Murray A,Mahboudi F,McMaster WR

doi

10.1016/j.vaccine.2004.08.032

subject

Has Abstract

pub_date

2005-01-19 00:00:00

pages

1170-7

issue

9

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(04)00643-7

journal_volume

23

pub_type

杂志文章

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