Reversible contraceptive effect of PH-20 immunization in male guinea pigs

Abstract

Sperm proteins are currently being studied as antigens on which to base a contraceptive vaccine. Sperm plasma membrane proteins offer the theoretical possibility of immunizing either males or females and achieving a contraceptive effect. In this study, we investigated the sperm plasma membrane protein PH-20 as an antigen for inducing infertility in males. We found that infertility can reproducibly be induced in male guinea pigs immunized with purified PH-20: 100% (29 of 29) of PH-20-immunized males became infertile, whereas all 22 controls were fertile. The males were extremely responsive to PH-20 immunization: infertility could be induced with a single injection of only 5 μg PH-20. Among males that received their initial injection when they were ~300 g (body weight), 14 of 15 had regained fertility at about 1 yr after initial injection. Surprisingly, in another group of males that received their first injection when they were ~650 g (body weight), only 1 of 5 had regained fertility about 1 yr after initial injection. Anti-PH-20 titers in antisera (2 mo after initial injection) were generally in the range 1.1-4.2 x 104 in twice-injected males and the range 1.8-9.4 x 103 in once-injected males. Over the next 6-11 mo, twice-injected males' titers decreased ≤ 4-fold, whereas once-injected males' titers decreased slightly (1.1- to 1.8-fold). After 6-11 mo, anti-PH-20 titers were in the range 1.0-4.8 x 103, and the precise residual titer did not correlate with fertility/infertility. The results show that immunization of males with PH-20, even at low doses, results in a reproducible, completely effective contraceptive action.