title: Co-administration of interleukins 7 and 15 with DNA vaccine improves protective immunity against Toxoplasma gondii.
abstract: Toxoplasma gondii is an obligatory intracellular parasite, which can infect all warm-blooded animals including humans. Cytokines, including IL-15 and IL-7, play a critical role in the regulation of the homeostasis of naive and memory T cells. Co-administration the DNA vaccine with cytokines may improve its efficacy. IL-7 and IL-15 from splenic tissues of Kunming mice were cloned, and eukaryotic plasmid pVAX-IL-7-IL-15 was constructed. Kunming mice were administrated with DNA vaccine expressing T. gondii calcium-dependent protein kinase 1 (TgCDPK1), pVAX-CDPK1, in the presence or absence of IL-7 and IL-15 plasmids (pVAX-IL-7-IL-15), immune responses were analyzed including lymphoproliferative assay, cytokine and serum antibody measurements, flow cytometric surface markers on lymphocytes, and thus protective immunity against acute and chronic T. gondii infection was estimated. Mice injected with pVAX-CDPK1 supplemented with pVAX-IL-7-IL-15 showed higher Toxoplasma-specific IgG2a titers, Th1 responses associated with the production of IFN-γ, IL-2 as well as cell-mediated cytotoxic activity where stronger frequencies of IFN-γ secreting CD8+ and CD4+ T cells (CD8+/CD4+ IFN-γ+ T cells) compared to controls. Co-administration of pVAX-IL-7-IL-15 and pVAX-CDPK1 significantly (P < 0.05) increased survival time (18.07 ± 5.43 days) compared with pVAX-CDPK1 (14.13 ± 3.85 days) or pVAX-IL-7-IL-15 (11.73 ± 1.83 days) alone, and pVAX-IL-7-IL-15 + pVAX-CDPK1 significantly reduced the number of brain cysts (73.5%) in contrast to pVAX-CDPK1 (46.0%) or pVAX-IL-7-IL-15 alone (45.0%). Our results indicate that supplementation of DNA vaccine with IL-7 and IL-15 would facilitate specific humoral and cellular immune responses elicited by DNA vaccine against acute and chronic T. gondii infection in mice.
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, PR China; Ningbo University School of Medicine, Ningbo, Zhejiang province 315211, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, PR China.
authors.forename: Zhong-Yuan
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases and Clinical Microbiology, Institute for Clinical Medicine, Faculty of Health Sciences, Aarhus University, Aarhus, Denmark.
authors.forename: Eskild
authors.initials: E
authors.lastname: Petersen
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, PR China.
authors.forename: Wen-Ge
authors.initials: WG
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, PR China; Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University College of Veterinary Medicine, Yangzhou, Jiangsu Province 225009, PR China. Electronic address: xingquanzhu1@hotmail.com.
authors.forename: Xing-Quan
authors.initials: XQ
authors.lastname: Zhu
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000592:standards; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000097:blood; D002460:Cell Line; D005260:Female; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D019409:Interleukin-15 / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D015851:Interleukin-7 / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D010957:Plasmids / Q000008:administration & dosage; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000592:standards*; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016019:Survival Analysis; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000592:standards*
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D019409:Interleukin-15; D015851:Interleukin-7; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma
keywords: DNA vaccine; Protective immunity; TgCDPK1; Toxoplasma gondii; Toxoplasmosis; pVAX-IL-7-IL-15