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In vivo Imaging of Transgenic Leishmania Parasites in a Live Host
Published on: July 27, 2010
Altered virulence and vaccination properties of Leishmania parasites grown in infected vaccinated mice
1Department of Surgery, Mount Sinai Research Institute, Toronto, Ontario, Canada.
Abstract:
BALB/c mice, which are normally highly susceptible to growth of Leishmania mexicana parasites in vivo, can be vaccinated with avirulent temperature-sensitive mutants of L. mexicana so that challenge with virulent organisms results in markedly diminished growth of the latter. Parasites extracted from the lesions which do appear in these mice are able to produce active infection in secondary hosts, although the rate of progression of these lesions is slower than that seen with the original virulent cloned organism. Interestingly, when irradiated parasites from the secondary hosts are themselves used to vaccinate naive BALB/c mice, less protection is seen than when irradiated virulent organisms from the initial infecting clone are used. These data suggest that when infection does take place in mice vaccinated with avirulent clones of parasite, the organisms which develop in lesions in these animals are substantially modified from those present in the initial infecting inoculum.
Insights
Vaccinating BALB/c mice with avirulent Leishmania mexicana mutants offers protection against virulent strains. However, parasites from lesions in vaccinated mice show reduced efficacy when used for subsequent vaccination, indicating modification.
Area of Science:
- Immunology
- Parasitology
- Infectious Diseases
Background:
- BALB/c mice are highly susceptible to Leishmania mexicana infections.
- Vaccination with avirulent parasite mutants can induce protection against virulent Leishmania mexicana.
Purpose of the Study:
- To investigate the protective efficacy of vaccination with avirulent Leishmania mexicana mutants in BALB/c mice.
- To characterize the immunogenicity of Leishmania mexicana parasites developing in lesions of vaccinated mice.
Main Methods:
- Vaccination of BALB/c mice with temperature-sensitive avirulent Leishmania mexicana mutants.
- Challenge with virulent Leishmania mexicana.
- Isolation and characterization of parasites from lesions in vaccinated mice.
- Secondary vaccination experiments using irradiated parasites from lesions.
Main Results:
- Vaccination with avirulent mutants significantly diminished the growth of virulent Leishmania mexicana upon challenge.
- Parasites from lesions in vaccinated mice could establish infection in secondary hosts but progressed slower.
- Irradiated parasites from secondary hosts elicited less protection than irradiated virulent parasites from the initial clone.
Conclusions:
- Vaccination with avirulent Leishmania mexicana mutants confers protection in susceptible BALB/c mice.
- Parasites developing in lesions of vaccinated mice are modified and exhibit altered immunogenicity.
- These findings suggest potential for vaccine development and understanding parasite adaptation during infection.
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