title: KSAC, a defined Leishmania antigen, plus adjuvant protects against the virulence of L. major transmitted by its natural vector Phlebotomus duboscqi.
abstract: BACKGROUND
  Recombinant KSAC and L110f are promising Leishmania vaccine candidates. Both antigens formulated in stable emulsions (SE) with the natural TLR4 agonist MPL® and L110f with the synthetic TLR4 agonist GLA in SE protected BALB/c mice against L. major infection following needle challenge. Considering the virulence of vector-transmitted Leishmania infections, we vaccinated BALB/c mice with either KSAC+GLA-SE or L110f+GLA-SE to assess protection against L. major transmitted via its vector Phlebotomus duboscqi.
  
  
  METHODS
  Mice receiving the KSAC or L110f vaccines were challenged by needle or L. major-infected sand flies. Weekly disease progression and terminal parasite loads were determined. Immunological responses to KSAC, L110f, or soluble Leishmania antigen (SLA) were assessed throughout vaccination, three and twelve weeks after immunization, and one week post-challenge.
  
  
  RESULTS
  Following sand fly challenge, KSAC-vaccinated mice were protected while L110f-vaccinated animals showed partial protection. Protection correlated with the ability of SLA to induce IFN-γ-producing CD4(+)CD62L(low)CCR7(low) effector memory T cells pre- and post-sand fly challenge.
  
  
  CONCLUSIONS
  This study demonstrates the protective efficacy of KSAC+GLA-SE against sand fly challenge; the importance of vector-transmitted challenge in evaluating vaccine candidates against Leishmania infection; and the necessity of a rapid potent Th1 response against Leishmania to attain true protection.
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, United States of America.
authors.forename: Regis
authors.initials: R
authors.lastname: Gomes
authors.forename: Clarissa
authors.initials: C
authors.lastname: Teixeira
authors.forename: Fabiano
authors.initials: F
authors.lastname: Oliveira
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Lawyer
authors.forename: Dia-Eldin
authors.initials: DE
authors.lastname: Elnaiem
authors.forename: Claudio
authors.initials: C
authors.lastname: Meneses
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Goto
authors.forename: Ajay
authors.initials: A
authors.lastname: Bhatia
authors.forename: Randall F
authors.initials: RF
authors.lastname: Howard
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Valenzuela
authors.forename: Shaden
authors.initials: S
authors.lastname: Kamhawi
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control* / Q000635:transmission; D051379:Mice; D008807:Mice, Inbred BALB C; D059208:Parasite Load; D010691:Phlebotomus / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D054332:Leishmaniasis Vaccines; D007371:Interferon-gamma