title: Protective efficacy of a  Treponema pallidum  Gpd DNA vaccine vectored by chitosan nanoparticles and fused with interleukin-2.
abstract: In the present study, immunomodulatory responses of a DNA vaccine constructed by fusing  Treponema pallidum  (Tp) glycerophosphodiester phosphodiesterase (Gpd) to interleukin-2 (IL-2) and using chitosan (CS) nanoparticles as vectors were investigated. New Zealand white rabbits were immunized by intramuscular inoculation of control DNAs, Tp Gpd DNA vaccine, or Gpd-IL-2 fusion DNA vaccine, which were vectored by CS nanoparticles. Levels of the anti-Gpd antibodies and levels of IL-2 and interferon-γ in rabbits were increased upon inoculation of Gpd-IL-2 fusion DNA vaccine, when compared with the inoculation with Gpd DNA vaccine, with CS vectoring increasing the effects. The Gpd-IL-2 fusion DNA vaccine efficiently enhanced the antigen-specific lymphocyte proliferative response. When the rabbits were challenged intradermally with 10(5) Tp (Nichols) spirochetes, the Gpd-IL-2 fusion DNA vaccine conferred better protection than the Gpd DNA vaccine (P < 0.05), as characterized by lower detectable amounts of dark field positive lesions (17.5%), lower ulcerative lesion scores (15%), and faster recovery. Individuals treated with the Tp Gpd-IL-2 fusion DNA vaccine vectored by CS nanoparticles had the lowest amounts of dark field positive lesions (10%) and ulcerations (5%) observed and the fastest recovery (42 days). These results indicate that the Gpd-IL-2 fusion DNA vaccine vectored by CS nanoparticles can efficiently induce Th1-dominant immune responses, improve protective efficacy against Tp spirochete infection, and effectively attenuate development of syphilitic lesions.
authors.affiliation: Pathogenic Biology Institute, University of South China, Hengyang, People's Republic of China.
authors.forename: Feijun
authors.initials: F
authors.lastname: Zhao
authors.forename: Shiping
authors.initials: S
authors.lastname: Wang
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhang
authors.forename: Weiming
authors.initials: W
authors.lastname: Gu
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.forename: Shuangquan
authors.initials: S
authors.lastname: Liu
authors.forename: Tiebing
authors.initials: T
authors.lastname: Zeng
authors.forename: Yuejun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yimou
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005822:Genetic Vectors; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000737:chemistry* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011817:Rabbits; D013587:Syphilis / Q000378:metabolism / Q000517:prevention & control*; D014210:Treponema pallidum / Q000235:genetics*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D007376:Interleukin-2; D019444:Vaccines, DNA; D007371:Interferon-gamma; D048271:Chitosan