Coadministration of Interleukin 12 Expression Vector with Antigen 2 cDNA Enhances Induction of Protective Immunity againstCoccidioides immitis

Abstract

Interleukin 12 (IL-12) plays an important role in the induction of protective immunity against cancer and infectious diseases. In this study we asked whether IL-12 cDNA could increase the protective capacity of the antigen 2 (Ag2) gene vaccine in experimental coccidioidomycosis. Coimmunization of BALB/c mice with a single-chain IL-12 cDNA (p40-L-p35) and Ag2 cDNA, both subcloned into the pVR1012 plasmid, significantly enhanced protection against systemic challenge with 2,500 arthroconidia, as evidenced by a greater-than-1.3-log-unit reduction in the fungal load in the lungs and spleens compared to mice receiving the pVR1012 vector alone, Ag2 cDNA alone, or IL-12 cDNA alone. The enhanced protection was associated with increased gamma interferon secretion; production of immunoglobulin G2a (IgG2a), IgG2b, and IgG3 antibodies to Coccidioides immitis antigen; and the influx of CD4+ and CD8+ T cells in lungs and spleens. When challenged by the pulmonary route, mice covaccinated with Ag2 cDNA and IL-12 cDNA were not protected at the lung level but did show a significant reduction in the fungal load in their livers and spleens compared to mice vaccinated with Ag2 cDNA or IL-12 cDNA alone. These results suggest that IL-12 acts as a therapeutic adjuvant to enhance Ag2 cDNA-induced protective immunity against experimental coccidioidomycosis through the induction of Th1-associated immune responses.

Absence of CD4+ T Cells Impairs Host Defence of Mice Infected with Fonsecaea pedrosoi

“…The importance of cell‐mediated immunity has been documented in the host defence against infection with various fungi including Cryptococcus neoformans [14], Coccidioides immitis [15], Paracoccidioides brasiliensis [16], Histoplasma capsulatum [17], Blastomyces dermatitidis [18], Sporothrix schenckii [19] and Candida albicans [20]. The cellular immune response on chromoblastomycosis has been little studied.…”

Experimental Animal Models of Coccidioidomycosis

“…68 With advances in laboratory technology, vaccine preparations for prevention of coccidioidomycosis have focused on subcellular and more recently to specifically cloned antigens, as well as improved ways to present the antigens, the use of engineered chimeric proteins and different adjuvants, many of which have shown some protective activity. 34,56,[69][70][71][72][73][74][75][76][77][78][79][80][81][82][83] These studies have primarily used mouse models of infection and have been performed by pretreatment of the mice with the vaccine preparation, usually multiple doses given subcutaneously, intramuscularly, or intraperitoneally, and challenged by intraperitoneal or pulmonary route 2 to 4 weeks later. Evaluation of protection is then based on prolonged survival and in some studies on the number of CFUs of Coccidioides remaining in the target organs (e.g., lungs).…”

Expression of a single‐chain human interleukin‐12 gene in transgenic tobacco plants and functional studies

“…Interleukin-12 has also been used as an adjuvant to induce systemic (Noguchi et al, 1995) and mucosal immunity (Boyaka et al, 1999). When co-administered with the corresponding antigens, it enhances induction of protective immunity against pathogens such as HIV (Gherardi et al, 1999), herpes simplex virus (Sin et al, 1999), Mycobacterium tuberculosis (Palendira et al, 2002), and Coccidioides immitis (Jiang et al, 1999b).…”