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.