title: A Listeria monocytogenes-based vaccine that secretes sand fly salivary protein LJM11 confers long-term protection against vector-transmitted Leishmania major.
abstract: Cutaneous leishmaniasis is a sand fly-transmitted disease characterized by skin ulcers that carry significant scarring and social stigmatization. Over the past years, there has been cumulative evidence that immunity to specific sand fly salivary proteins confers a significant level of protection against leishmaniasis. In this study, we used an attenuated strain of Listeria monocytogenes as a vaccine expression system for LJM11, a sand fly salivary protein identified as a good vaccine candidate. We observed that mice were best protected against an intradermal needle challenge with Leishmania major and sand fly saliva when vaccinated intravenously. However, this protection was short-lived. Importantly, groups of vaccinated mice were protected long term when challenged with infected sand flies. Protection correlated with smaller lesion size, fewer scars, and better parasite control between 2 and 6 weeks postchallenge compared to the control group of mice vaccinated with the parent L. monocytogenes strain not expressing LJM11. Moreover, protection correlated with high numbers of CD4(+), gamma interferon-positive (IFN-γ(+)), tumor necrosis factor alpha-positive/negative (TNF-α(+/-)), interleukin-10-negative (IL-10(-)) cells and low numbers of CD4(+) IFN-γ(+/-) TNF-α(-) IL-10(+) T cells at 2 weeks postchallenge. Overall, our data indicate that delivery of LJM11 by Listeria is a promising vaccination strategy against cutaneous leishmaniasis inducing long-term protection against ulcer formation following a natural challenge with infected sand flies.
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA.
authors.forename: Delbert S
authors.initials: DS
authors.lastname: Abi Abdallah
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Pavinski Bitar
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
authors.forename: Fabiano
authors.initials: F
authors.lastname: Oliveira
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
authors.forename: Claudio
authors.initials: C
authors.lastname: Meneses
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Park
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA Baker Institute for Animal Health, Cornell University, Ithaca, New York, USA.
authors.forename: Susana
authors.initials: S
authors.lastname: Mendez
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
authors.forename: Shaden
authors.initials: S
authors.lastname: Kamhawi
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Valenzuela
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA hm72@cornell.edu.
authors.forename: Hélène
authors.initials: H
authors.lastname: Marquis
mesh_terms: D000818:Animals; D001733:Bites and Stings / Q000276:immunology / Q000469:parasitology; D004431:Ear, External / Q000276:immunology / Q000469:parasitology; D019476:Insect Proteins / Q000276:immunology*; D007303:Insect Vectors / Q000469:parasitology; D018320:Leishmania major / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000517:prevention & control*; D008089:Listeria monocytogenes; D051379:Mice; D008810:Mice, Inbred C57BL; D011576:Psychodidae / Q000502:physiology*; D012471:Salivary Proteins and Peptides / Q000276:immunology*; D013601:T-Lymphocytes / Q000145:classification; D014614:Vaccines, Synthetic
chemical_list: D019476:Insect Proteins; D054332:Leishmaniasis Vaccines; D012471:Salivary Proteins and Peptides; D014614:Vaccines, Synthetic
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