Killed but Metabolically Active Leishmania infantum as a Novel Whole-Cell Vaccine for Visceral Leishmaniasis

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

doi:10.1128/CVI.05660-11

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Killed but Metabolically Active Leishmania infantum as a Novel Whole-Cell Vaccine for Visceral Leishmaniasis

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Killed but Metabolically Active Leishmania infantum as a Novel Whole-Cell Vaccine for Visceral Leishmaniasis

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, …

Clinical and vaccine immunology, Vol.19(4), pp.490-498

04/2012

DOI: 10.1128/CVI.05660-11

PMCID: PMC3318268

PMID: 22323556

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Abstract

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.

Vaccines

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Title: Subtitle: Killed but Metabolically Active Leishmania infantum as a Novel Whole-Cell Vaccine for Visceral Leishmaniasis
Creators: Kevin W Bruhn - David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
Ron Birnbaum - Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, California, USA
Jacquelyn Haskell - Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, California, USA
Veena Vanchinathan - Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, California, USA
Stephanie Greger - Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, California, USA
Rupa Narayan - Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, California, USA
Pei-Lin Chang - Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, California, USA
Thu Anh Tran - Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, California, USA
Suzanne M Hickerson - Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri, USA
Stephen M Beverley - Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri, USA
Mary E Wilson - Departments of Internal Medicine, Epidemiology and Microbiology, University of Iowa and the Veterans Affairs Medical Center, Iowa City, Iowa, USA
Noah Craft - David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
Resource Type: Journal article
Publication Details: Clinical and vaccine immunology, Vol.19(4), pp.490-498
Publisher: American Society for Microbiology; 1752 N St., N.W., Washington, DC
DOI: 10.1128/CVI.05660-11
PMID: 22323556
PMCID: PMC3318268
ISSN: 1556-6811
eISSN: 1556-679X
Language: English
Date published: 04/2012
Academic Unit: Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
Record Identifier: 9984001161302771

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