title: Coadministration of interleukin 12 expression vector with antigen 2 cDNA enhances induction of protective immunity against Coccidioides 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.
authors.affiliation: Department of Clinical Investigation, Texas Center for Infectious Disease, San Antonio, Texas 78223, USA.
authors.forename: C
authors.initials: C
authors.lastname: Jiang
authors.forename: D M
authors.initials: DM
authors.lastname: Magee
authors.forename: R A
authors.initials: RA
authors.lastname: Cox
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood; D000946:Antigens, Fungal / Q000235:genetics*; D003045:Coccidioides / Q000276:immunology*; D018076:DNA, Complementary / Q000276:immunology*; D005260:Female; D005656:Fungal Proteins; D005657:Fungal Vaccines / Q000276:immunology*; D006023:Glycoproteins / Q000235:genetics* / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000235:genetics*; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D018076:DNA, Complementary; D005656:Fungal Proteins; D005657:Fungal Vaccines; D006023:Glycoproteins; D007074:Immunoglobulin G; D019444:Vaccines, DNA; C102758:antigen 2, Coccidioides; D018664:Interleukin-12; D007371:Interferon-gamma