| Autor: |
Bruhn, Kevin W., Birnbaum, Ron, Haskell, Jacquelyn, Vanchinathan, Veena, Greger, Stephanie, Narayan, Rupa, Chang, Pei-Lin, Tran, Thu Anh, Hickerson, Suzanne M., Beverley, Stephen M., Wilson, Mary E., Craft, Noah |
| Zdroj: |
Clinical and Vaccine Immunology (formerly CDLI); February 2012, Vol. 19 Issue: 4 p490-498, 9p |
| Abstrakt: |
ABSTRACTThere are currently no effective vaccines for visceral leishmaniasis, the second most deadly parasitic infection in the world. Here, we describe a novel whole-cell vaccine approach using Leishmania infantum chagasipromastigotes treated with the psoralen compound amotosalen (S-59) and low doses of UV A radiation. This treatment generates permanent, covalent DNA cross-links within parasites and results in Leishmaniaorganisms termed killed but metabolically active (KBMA). In this report, we characterize the in vitrogrowth characteristics of both KBMA L. majorand KBMA L. infantum chagasi. Concentrations of S-59 that generate optimally attenuated parasites were identified. Like live L. infantum chagasi, KBMA L. infantum chagasiparasites were able to initially enter liver cells in vivoafter intravenous infection. However, whereas live L. infantum chagasiinfection leads to hepatosplenomegaly in mice after 6 months, KBMA L. infantum chagasiparasites were undetectable in the organs of mice at this time point. In vitro, KBMA L. infantum chagasiretained the ability to enter macrophages and induce nitric oxide production. These characteristics of KBMA L. infantum chagasicorrelated with the ability to prophylactically protect mice via subcutaneous vaccination at levels similar to vaccination with live, virulent organisms. Splenocytes from mice vaccinated with either live L. infantum chagasior KBMA L. infantum chagasidisplayed similar cytokine patterns in vitro. These results suggest that KBMA technology is a potentially safe and effective novel vaccine strategy against the intracellular protozoan L. infantum chagasi. This approach may represent a new method for whole-cell vaccination against other complex intracellular pathogens. |
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