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ZP3 peptide vaccine that induces antibody and reversible infertility without autoimmune oophoritis
1Department of Pathology, University of Virginia, Charlottesville 22908, USA.
Autoantibodies to ZP3, a major glycoprotein of the zona pellucida (ZP) with sperm receptor function, can block sperm/oocyte interaction. However, only mice of certain major histocompatibility complex (MHC) haplotype respond to the ZP3 peptide. Moreover, ZP3-specific T cells can mediate ovarian autoimmune disease. A chimeric peptide has been designed that induces antibody to native ZP3 regardless of the MHC haplotype of the inbred mice tested. This results in reduction in fertility that is reversible. Infertility correlates well with ZP antibody titer, and the mice do not develop concomitant autoimmune oophoritis. The vaccine contains (1) a promiscuous foreign T-cell peptide capable of eliciting a T-cell response regardless of the animals' MHC haplotype, and (2) a modified native B-cell peptide of ZP3.
Autoantibodies to ZP3, a major glycoprotein of the zona pellucida (ZP) with sperm receptor function, can block sperm/oocyte interaction. However, only mice of certain major histocompatibility complex (MHC) haplotype respond to the ZP3 peptide. Moreover, ZP3-specific T cells can mediate ovarian autoimmune disease. A chimeric peptide has been designed that induces antibody to native ZP3 regardless of the MHC haplotype of the inbred mice tested. This results in reduction in fertility that is reversible. Infertility correlates well with ZP antibody titer, and the mice do not develop concomitant autoimmune oophoritis. The vaccine contains (1) a promiscuous foreign T-cell peptide capable of eliciting a T-cell response regardless of the animals' MHC haplotype, and (2) a modified native B-cell peptide of ZP3.