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

Nancy Gore Saravia, Blanca Escorcia, Yaneth Osorio, Liliana Valderrama, Darren Brooks, Lourdes Arteaga, Graham Coombs, Jeremy Mottram, Bruno Luis Travi

Research output: Contribution to journalArticle

36 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4247-4259
Number of pages13
JournalVaccine
Volume24
Issue number19
DOIs
StatePublished - May 8 2006
Externally publishedYes

Keywords

  • Cysteine proteinases
  • Golden hamster
  • Leishmania
  • Live-attenuated vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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    Saravia, N. G., Escorcia, B., Osorio, Y., Valderrama, L., Brooks, D., Arteaga, L., Coombs, G., Mottram, J., & Travi, B. L. (2006). Pathogenicity and protective immunogenicity of cysteine proteinase-deficient mutants of Leishmania mexicana in non-murine models. Vaccine, 24(19), 4247-4259. https://doi.org/10.1016/j.vaccine.2005.05.045