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Killed butMetabolically ActiveLeishmania infantumas a Novel Whole-CellVaccine for VisceralLeishmaniasis Kevin W. BruhnRon BirnbaumJacquelyn Haskell2012 год

Killed but Metabolically Active Leishmania infantum as a Novel Whole-Cell Vaccine for Visceral Leishmaniasis
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Аннотация: There 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 chagasi promastigotes 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 Leishmania organisms termed killed but metabolically active (KBMA). In this report, we characterize the in vitro growth characteristics of both KBMA L. major and KBMA L. infantum chagasi. Concentrations of S-59 that generate optimally attenuated parasites were identified. Like live L. infantum chagasi, KBMA L. infantum chagasi parasites were able to initially enter liver cells in vivo after intravenous infection. However, whereas live L. infantum chagasi infection leads to hepatosplenomegaly in mice after 6 months, KBMA L. infantum chagasi parasites were undetectable in the organs of mice at this time point. In vitro, KBMA L. infantum chagasi retained the ability to enter macrophages and induce nitric oxide production. These characteristics of KBMA L. infantum chagasi correlated 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 chagasi or KBMA L. infantum chagasi displayed 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.
Год издания: 2012
Авторы: Kevin W. Bruhn, Ron Birnbaum, Jacquelyn Haskell, Veena Vanchinathan, Stephanie Greger, Rupa Narayan, Pei-Lin Chang, Thu Anh Tran, Suzanne M. Hickerson, Stephen M. Beverley, Mary E. Wilson, Noah Craft
Издательство: American Society for Microbiology
Источник: Clinical and Vaccine Immunology
Ключевые слова: Research on Leishmaniasis Studies, Trypanosoma species research and implications
Другие ссылки: Clinical and Vaccine Immunology (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)