Discovery of human posterior head 20 (hPH20) and homo sapiens sperm acrosome associated 1 (hSPACA1) immunocontraceptive epitopes and their effects on fertility in male and female mice
Xuemei Chen A , Xiaodong Liu A , Xiuhua Ren A , Xuewu Li B , Li Wang C and Weidong Zang A D
+ Author Affiliations
- Author Affiliations
A Department of Human Anatomy, Basic Medical College of Zhengzhou University, Number 100, Kexue Road, Zhengzhou 450001, Henan, China.
B Key Laboratory of Animal Immunology of the Ministry of Agriculture, Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, Henan, China.
C Department of Pathogenic Microorganism, Basic Medical College of Zhengzhou University, Number 100, Kexue Road, Zhengzhou 450001, Henan, China.
D Corresponding author. Email: zwd@zzu.edu.cn
Reproduction, Fertility and Development 28(4) 416-427 https://doi.org/10.1071/RD14134
Submitted: 13 May 2014 Accepted: 13 June 2014 Published: 11 September 2014
Abstract
The key goals of immunocontraception research are to obtain full contraceptive effects using vaccines administered to both males and females. Current research concerning human anti-sperm contraceptive vaccines is focused on delineating infertility-related epitopes to avoid autoimmune disease. We constructed phage-display peptide libraries to select epitope peptides derived from human posterior head 20 (hPH20) and homo sapiens sperm acrosome associated 1 (hSPACA1) using sera collected from infertile women harbouring anti-sperm antibodies. Following five rounds of selection, positive colonies were reconfirmed for reactivity with the immunoinfertile sera. We biopanned and analysed the chemical properties of four epitope peptides, named P82, Sa6, Sa37 and Sa76. Synthetic peptides were made and coupled to either bovine serum albumin (BSA) or ovalbumin. We used the BSA-conjugated peptides to immunise BALB/c mice and examined the effects on fertility in female and male mice. The synthetic peptides generated a sperm-specific antibody response in female and male mice that caused a contraceptive state. The immunocontraceptive effect was reversible and, with the disappearance of peptide-specific antibodies, there was complete restoration of fertility. Vaccinations using P82, Sa6 and Sa76 peptides resulted in no apparent side effects. Thus, it is efficient and practical to identify epitope peptide candidates by phage display. These peptides may find clinical application in the specific diagnosis and treatment of male and female infertility and contraceptive vaccine development.
Additional keywords: anti-sperm antibodies (ASAs), gene-specific peptide libraries, immunocontraceptive vaccine, immunoinfertile, male and female mice, phage display, sperm, synthetic peptide.
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