A Chimeric Sperm Peptide Induces Antibodies and Strain-Specific Reversible Infertility in Mice¹

^a Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 ^b Department of Pharmacology, NV Organon, 5340 BH Oss, The Netherlands

The development of a contraceptive vaccine based on a gamete-specific antigen requires knowledge of the ability of the antigen to elicit an immune response that inhibits fertilization. A well-defined immune response, as elicited by a synthetic peptide comprising a dominant B-cell epitope coupled to a common promiscuous T-cell epitope, might be preferable. In this study, the immunodominant B-cell epitope of sperm antigen Sp17 has been identified and synthesized as a chimeric peptide with the promiscuous T-cell epitope bovine RNase[94–104] at the N terminal. Immunization of female BALB/c mice with this peptide induced a dose-dependent reduction in fertility. Although antibodies to recombinant and native Sp17 were elicited in these mice, there was no strict correlation between the level of these antibodies and the reduction in fertility. Moreover, the induction of infertility was strain-specific since no effect on fertility could be induced in B6AF1 mice. To understand the mechanism behind this apparent strain-specific infertility induction, a more extended study on both the humoral and the cellular immune response to the chimeric peptide was performed. The antigen-specific T-cell response and the levels of antigen-specific cytokines are the major factors that affect fertility outcome.

¹ This work was supported by a National Institutes of Health grant and postdoctoral fellowship through the Center for Recombinant Gamete Vaccinogens, University of Virginia and United States Public Health Service (U54HD29099), Bethesda, MD, and by an Organon Research Agreement.

² Correspondence: M.G. O'Rand, Department of Cell Biology & Anatomy, University of North Carolina at Chapel Hill, CB #7090, 210 Taylor Hall, Chapel Hill, NC 27599-7090. FAX: (919) 966-1856; morand{at}unc.edu

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