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Enhanced contraceptive response by co‐immunization of DNA and protein vaccines encoding the mouse zona pellucida 3 with minimal oophoritis in mouse ovary
Author(s) -
Li Jinyao,
Jin Huali,
Zhang Ailian,
Li Yijie,
Wang Bin,
Zhang Fuchun
Publication year - 2007
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1069
Subject(s) - zona pellucida , immunization , zona pellucida glycoprotein , follicular phase , dna vaccination , immunology , biology , antibody , epitope , foxp3 , andrology , immune system , medicine , oocyte , endocrinology , embryo , genetics
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.