title: Nanomaterial-dependent immunoregulation of dendritic cells and its effects on biological activities of contraceptive nanovaccines.
abstract: Nanovehicles are promising delivery systems for various vaccines. Nevertheless, different biophysicochemical properties of nanoparticles (NPs), dominating their in vitro and in vivo performances for vaccination, remain unclear. We attempted to elucidate the effects of NPs and their pH-sensitivity on in vitro and in vivo efficacy of resulting prophylactic nanovaccines containing a contraceptive peptide (FSHR). To this end, pH-responsive and non-responsive nanovaccines were produced using acetalated β-cyclodextrin (Ac-bCD) and poly(lactic-co-glycolic acid) (PLGA), respectively. Meanwhile, FSHR derived from an epitope of the follicle-stimulating hormone receptor was used as the model antigen. FSHR-containing Ac-bCD and PLGA NPs were successfully prepared by a nanoemulsion technique, leading to well-shaped nanovaccines with high loading efficiency. The pH-sensitivity of Ac-bCD and PLGA nanovaccines was examined by in vitro hydrolysis and antigen release studies. Nanovaccines could be effectively engulfed by dendritic cells (DCs) via endocytosis in both dose and time dependent manners, and their intracellular trafficking was closely related to the pH-sensitivity of the carrier materials. Furthermore, nanovaccines could induce the secretion of inflammatory cytokines by DCs and T cells co-cultured with the stimulated DCs. In vivo evaluations demonstrated that nanovaccines were more potent than that based on the complete Freund's adjuvant, with respect to inducing anti-FSHR antibody, reducing the sperm count, inhibiting the sperm motility, and increasing the teratosperm rate. Immunization of male mice with nanovaccines notably decreased the parturition incidence of the mated females. Consequently, both in vitro and in vivo activities of FSHR could be considerably augmented by NPs. More importantly, our studies indicated that the pH-responsive nanovaccine was not superior over the non-responsive counterpart for the examined peptide antigen.
authors.affiliation: Department of Obstetrics and Gynaecology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing 400038, China; Department of Obstetrics and Gynaecology, Hospital 81 of PLA, Nanjing 210002, China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynaecology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Obstetrics and Gynaecology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Luping
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics and Gynaecology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Department of Obstetrics and Gynaecology, Tangshan Workers' Hospital of Hebei Province, Tangshan 063000, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Dinglin
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Shibin
authors.initials: S
authors.lastname: Feng
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynaecology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Obstetrics and Gynaecology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China.
authors.forename: Ruibing
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing 400038, China. Electronic address: jxzhang1980@gmail.com.
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynaecology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: zhi.lzliang@gmail.com.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Liang
mesh_terms: D000818:Animals; D003270:Contraceptive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D065546:Drug Liberation; D005260:Female; D005298:Fertility / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000097:blood; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D008297:Male; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011962:Receptors, FSH / Q000737:chemistry / Q000276:immunology*; D013076:Sperm Count; D013081:Sperm Motility; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D003270:Contraceptive Agents; D016207:Cytokines; D007074:Immunoglobulin G; D010455:Peptides; D011962:Receptors, FSH; D014612:Vaccines; D047392:beta-Cyclodextrins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Cyclodextrin; Dendritic cell; Intracellular delivery; Nanoparticle; Peptide antigen; pH-responsive