Enhanced contraceptive response by co-immunization of DNA and protein vaccines encoding the mouse zona pellucida 3 with minimal oophoritis in mouse ovary

Authors

  • Jinyao Li,

    1. Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, 830046, P.R. China
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  • Huali Jin,

    1. State Key Laboratory for Agro-Biotechnology, Department of Microbiology and Immunology, College of Biological Science, China Agricultural University, Beijing 100094, P.R. China
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  • Ailian Zhang,

    1. Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, 830046, P.R. China
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  • Yijie Li,

    1. Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, 830046, P.R. China
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  • Bin Wang,

    1. State Key Laboratory for Agro-Biotechnology, Department of Microbiology and Immunology, College of Biological Science, China Agricultural University, Beijing 100094, P.R. China
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  • Fuchun Zhang

    Corresponding author
    1. Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, 830046, P.R. China
    • Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, 830046, P.R. China.
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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-γ, 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. Copyright © 2007 John Wiley & Sons, Ltd.

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