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  • Title: Life-long systemic protection in mice vaccinated with L. major and adenovirus IL-12 vector requires active infection, macrophages and intact lymph nodes.
    Author: Gabaglia CR, Sercarz EE, Diaz-De-Durana Y, Hitt M, Graham FL, Gauldie J, Braciak TA.
    Journal: Vaccine; 2004 Nov 25; 23(2):247-57. PubMed ID: 15531044.
    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.
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