title: Enhanced contraceptive response by co-immunization of DNA and protein vaccines encoding the mouse zona pellucida 3 with minimal oophoritis in mouse ovary.
abstract: Zona pellucida 3 (ZP3) acts as the primary sperm receptor, induces autoantibody that can prevent oocyte fertilization and has been proposed as a vaccine candidate for contraception in humans. Due to the elicited autoreactive T cell inflammation that causes ovarian destruction, ZP3-based vaccine with removed T epitopes from the ZP3 is considered as a preferred approach. We present here a new strategy to eliminate the T cell inflammation while retaining a high level of antibody by co-immunization of mZP3 DNA and protein vaccines, which resulted in a higher reduction rate of fertility in this group. Histological analysis showed that there were normal follicular developments of infertile mice in the co-immunized group; while other vaccine groups of the most infertile mice lacked mature follicles. There was a significant correlation between normal follicular development and the inhibition of T cell response in co-immunized mice. At the same time, co-immunization reduced the production of inflammatory cytokine, IFN-gamma, and increased the productions of IL-10 and FoxP3 in CD4 T cells, suggesting the anti-inflammation may be via a T regulatory function. The results indicate that co-immunization of mZP3 DNA- and protein-based vaccines can reduce fertility without interfering with the normal follicular development and present a novel strategy to develop a contraceptive vaccine in humans.
authors.affiliation: Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, 830046, P R China.
authors.forename: Jinyao
authors.initials: J
authors.lastname: Li
authors.forename: Huali
authors.initials: H
authors.lastname: Jin
authors.forename: Ailian
authors.initials: A
authors.lastname: Zhang
authors.forename: Yijie
authors.initials: Y
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Fuchun
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001483:Base Sequence; D003267:Contraception / Q000592:standards*; D017931:DNA Primers; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D010053:Ovary / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*; D015044:Zona Pellucida / Q000276:immunology*
chemical_list: D017931:DNA Primers; D019444:Vaccines, DNA