Pathogenicity and protective immunogenicity of cysteine proteinase-deficient mutants of Leishmania mexicana in non-murine models

Saravia, NG, Escoria, B, Osorio, Y, Valderramaa, L, Brooks, DR, Arteaga, L, Coombs, GH, Mottram, JC and Travi, BL 2006, 'Pathogenicity and protective immunogenicity of cysteine proteinase-deficient mutants of Leishmania mexicana in non-murine models' , Vaccine, 24 (19) , pp. 4247-4259.

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Abstract

This study demonstrates that deletion of cysteine proteinase (CP) genes diminishes pathogenicity of Leishmania mexicana in non-murine experimental host models while preserving immunogenicity. Both cpb and cpa/cpb-deficient lines induced delayed disease onset, smaller lesions and lower parasite burden in hamsters. cpa/cpb-deficient L. mexicana grew more slowly as promastigotes and presented lower infectivity and growth in human mononuclear phagocytic host cells. Protection against homologous challenge comparable to that induced by infection with the virulent wild-type (WT) L. mexicana strain was achieved in the highly susceptible hamster model by immunization with 1000 cpb-deficient promastigotes. CP-deficient L. mexicana elicited significantly lower levels of Th2-associated cytokines IL-10 and TGF-β than the WT in the primary lesion of hamsters. These findings support the feasibility of using genetically attenuated live Leishmania to achieve protective immunity.

Item Type: Article
Themes: Subjects / Themes > Q Science > Q Science (General)
Subjects outside of the University Themes
Schools: Schools > School of Environment and Life Sciences
Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title: Vaccine
Publisher: Elsevier
Refereed: Yes
ISSN: 0264410X
Depositing User: H Kenna
Date Deposited: 07 Aug 2007 10:29
Last Modified: 27 Aug 2021 21:58
URI: https://usir.salford.ac.uk/id/eprint/130

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