Life-long systemic protection in mice vaccinated with L. major and adenovirus IL-12 vector requires active infection, macrophages and intact lymph nodes

• Published in: Vaccine 2004-11, Vol.23 (2), p.247-257
• Main Authors: Gabaglia, Claudia Raja, Sercarz, Eli E., Diaz-De-Durana, Yaiza, Hitt, Mary, Graham, Frank L., Gauldie, Jack, Braciak, Todd A.
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Adenovirus; Animals; Antigens, Protozoan - immunology; Applied microbiology; Biological and medical sciences; Cell Line; Fundamental and applied biological sciences. Psychology; Gene therapy; Genetic Vectors - administration & dosage; Interleukin-12 - genetics; Interleukin-12 - therapeutic use; Leishmania major; Leishmania major - genetics; Leishmania major - immunology; Leishmaniasis, Cutaneous - immunology; Leishmaniasis, Cutaneous - parasitology; Leishmaniasis, Cutaneous - prevention & control; Lymph Nodes - immunology; Macrophages; Macrophages - drug effects; Macrophages - immunology; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; T cell memory; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Synthetic - immunology; Virology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2004.05.012

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-γ 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.