title: Assessment of the immune responses to Treponema pallidum Gpd DNA vaccine adjuvanted with IL-2 and chitosan nanoparticles before and after Treponema pallidum challenge in rabbits.
abstract: Syphilis is a multistage, sexually transmitted disease caused by the spirochete, Treponema pallidum (Tp). A significantly high incidence of syphilis has been reported in several countries, including China, and there is an urgent need for the development of efficacious vaccines against syphilis. DNA vaccines are a major breakthrough in the field of vaccination with several advantages over traditional vaccines. Animal model studies of Tp DNA vaccines have not been reported elsewhere but our previous reports describe the development of a single-gene Tp DNA vaccine and preclinical immunization study. In this study, chitosan (CS) nanoparticles were used as a vector and an interleukin-2 expression plasmid (pIL-2) as an adjuvant to enhance a TpGpd DNA vaccine candidate (pTpGpd) in a rabbit Tp skin challenge model. At week 8 after the first immunization, three rabbits from each group were used to determine cytokine measurements and spleen lymphocyte proliferation assay. pTpGpd in combination with pIL-2 wrapped with CS led to the greatest enhancement of anti-TpGpd antibodies and T-cell proliferation. During infection, levels of anti-TpGpd antibodies and T-cell proliferation were measured. Both the serum special IgG and IL-2, interferon-γ were significantly increased by the co-injection of the IL-2 plasmid compared with the injection of TpGpd DNA alone (P<0.05). Furthermore, IL-2 plasmid coinjection efficiently enhanced the antigen-specific lymphocyte proliferation response. Additionally, the ratios of positive skin lesions and ulcer lesions in groups immunized with pTpGpd were significantly lower than those of the pIL-2, CS or pIL-2 mixed with CS control groups (P<0.001). CS vectored and pIL-2 adjuvanted pTpGpd immunized animals exhibited the lowest rates of positive skin tests (8.33%) and ulcer lesions (4.17%) and the fastest recovery (42 d). These experiments indicate that co-injection of a pIL-2 plasmid with pTpGpd DNA vaccine wrapped with CS can significantly strengthen the long-term stability of immune response during infection, efficiently improve the protective effect against T. pallidum spirochetes infection and attenuate syphilitic lesion development.
authors: Pathogenic Biology Institute, School of Medicine, University of South China, Hengyang 421001, China.
authors: Feijun
authors: F
authors: Zhao
authors: Xiaohong
authors: X
authors: Zhang
authors: Shuangquan
authors: S
authors: Liu
authors: Tiebing
authors: T
authors: Zeng
authors: Jian
authors: J
authors: Yu
authors: Weiming
authors: W
authors: Gu
authors: Yuejun
authors: Y
authors: Zhang
authors: Xi
authors: X
authors: Chen
authors: Yimou
authors: Y
authors: Wu
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000235:genetics; D048271:Chitosan / Q000008:administration & dosage; D004195:Disease Models, Animal; D005798:Genes, Bacterial; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage; D011817:Rabbits; D013587:Syphilis / Q000276:immunology / Q000517:prevention & control; D013601:T-Lymphocytes / Q000276:immunology; D014210:Treponema pallidum / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D007376:Interleukin-2; D019444:Vaccines, DNA; D007371:Interferon-gamma; D048271:Chitosan