title: Immunity to sand fly salivary protein LJM11 modulates host response to vector-transmitted leishmania conferring ulcer-free protection.
abstract: Leishmania vaccines that protect against needle challenge fail against the potency of a Leishmania-infected sand fly transmission. Here, we demonstrate that intradermal immunization of mice with 500 ng of the sand fly salivary recombinant protein LJM11 (rLJM11) from Lutzomyia longipalpis, in the absence of adjuvant, induces long-lasting immunity that results in ulcer-free protection against Leishmania major delivered by vector bites. This protection is antibody independent and abrogated by depletion of CD4(+) T cells. Two weeks after challenge, early induction of IFN-γ specifically to rLJM11 correlates to diminished parasite replication in protected animals. At this time point, Leishmania-specific induction of IFN-γ in these mice is low in comparison with its high level in non-protected controls. We hypothesize that early control of parasites in a T-cell helper type 1 environment induced by immunity to LJM11 permits the slow development of Leishmania-specific immunity in the absence of open ulcers. Leishmania-specific immunity observed 5 weeks after infection in rLJM11-immunized mice shows a twofold increase over controls in the percentage of IFN-γ-producing CD4(+) T cells. We propose LJM11 as an immunomodulator that drives an efficient and controlled protective immune response to a sand fly-transmitted Leishmania somewhat mimicking "leishmanization"-induced protective immunity but without its associated lesions.
authors: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.
authors: Regis
authors: R
authors: Gomes
authors: Fabiano
authors: F
authors: Oliveira
authors: Clarissa
authors: C
authors: Teixeira
authors: Claudio
authors: C
authors: Meneses
authors: Dana C
authors: DC
authors: Gilmore
authors: Dia-Eldin
authors: DE
authors: Elnaiem
authors: Shaden
authors: S
authors: Kamhawi
authors: Jesus G
authors: JG
authors: Valenzuela
mesh_terms: D000818:Animals; D001733:Bites and Stings / Q000276:immunology / Q000469:parasitology; D004195:Disease Models, Animal; D004431:Ear, External / Q000276:immunology / Q000469:parasitology; D057809:HEK293 Cells; D006801:Humans; D019476:Insect Proteins / Q000276:immunology / Q000494:pharmacology; D018320:Leishmania major / Q000254:growth & development / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000276:immunology* / Q000494:pharmacology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000517:prevention & control* / Q000635:transmission; D008198:Lymph Nodes / Q000276:immunology / Q000469:parasitology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011576:Psychodidae / Q000276:immunology* / Q000469:parasitology; D012463:Saliva / Q000276:immunology / Q000469:parasitology; D012471:Salivary Proteins and Peptides / Q000276:immunology*; D012883:Skin Ulcer / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000469:parasitology; D014614:Vaccines, Synthetic / Q000276:immunology / Q000494:pharmacology
chemical_list: D019476:Insect Proteins; D054332:Leishmaniasis Vaccines; D012471:Salivary Proteins and Peptides; D014614:Vaccines, Synthetic