title: Life-long systemic protection in mice vaccinated with L. major and adenovirus IL-12 vector requires active infection, macrophages and intact lymph nodes.
abstract: Immunization with soluble leishmanial antigen (SLA) in IFA plus Ad5IL-12 vector induced protection confined to the immunized footpad in BALB/c mice. However, animals that controlled a primary infection with a Leishmania major challenge in the same immunized footpad, became resistant to subsequent contralateral rechallenges due to expansion of IFN-gamma secreting cells. This systemic immunity could be disrupted either by macrophage depletion during immunization or by lymphadenectomy after challenge. We show that this procedure does not interfere with tissue-compartmentalized protection, since lymphadenectomized and splenectomized animals were resistant to rechallenges performed in the immunized footpads. Our results indicate that SLA-Ad5IL-12 vector priming requires macrophages to generate systemic protection. Furthermore, a previously undescribed lymphoid organ-independent, protective immune response is contained within the tissue microenvironment of the immunized/challenged footpad. These results have important implications for vaccine design against leishmanial and mycobacterial infections and diseases caused by intracellular pathogens.
authors.affiliation: Division of Immune Regulation, Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA. cgabaglia@tpims.org
authors.forename: Claudia Raja
authors.initials: CR
authors.lastname: Gabaglia
authors.forename: Eli E
authors.initials: EE
authors.lastname: Sercarz
authors.forename: Yaiza
authors.initials: Y
authors.lastname: Diaz-De-Durana
authors.forename: Mary
authors.initials: M
authors.lastname: Hitt
authors.forename: Frank L
authors.initials: FL
authors.lastname: Graham
authors.forename: Jack
authors.initials: J
authors.lastname: Gauldie
authors.forename: Todd A
authors.initials: TA
authors.lastname: Braciak
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D002460:Cell Line; D005822:Genetic Vectors / Q000008:administration & dosage; D018664:Interleukin-12 / Q000235:genetics / Q000627:therapeutic use*; D018320:Leishmania major / Q000235:genetics / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D008198:Lymph Nodes / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D014614:Vaccines, Synthetic; D018664:Interleukin-12