Male contraceptive shows promise in monkeys.

Women have numerous birth control methods to choose from, but men have only two main options: condoms or vasectomy. New research is pointing toward a third alternative, a shot that primes the immune system against a protein critical for reproduction.

Researchers have toyed with the idea of "immunocontraception" for decades, says Michael O'Rand of the University of North Carolina at Chapel Hill. But most immunocontraception experiments in animals have attempted to prompt antisperm immune reactions in females, a method that hasn't worked very well.

In search of something better, O'Rand and his colleagues examined proteins produced in the primate epididymis, a tube in the testes that stores sperm. They noticed that the epididymis adds the protein Eppin to the surface of sperm as they mature. Although the researchers don't know the protein's function, they speculated that Eppin might make a good target for immunocontraception in males.

O'Rand's team used synthetic Eppin as a vaccine in nine male macaques that already had fathered offspring. After seven of the animals developed high numbers of antibodies to Eppin, the researchers tested those monkeys' fertility. Despite frequent matings, none of these males impregnated females.

Because reversibility is an attractive feature of any contraception method, O'Rand's group investigated whether fertility returned after they stopped giving the monkeys booster shots. Of the seven monkeys tested, five impregnated a female within months of going off the vaccine. The researchers report their findings in the Nov. 12, 2004 Science.

O'Rand notes that investigators will need to answer several questions before testing the contraceptive vaccine in people, such as why some of the animals develop high antibodies to Eppin and others failed to regain fertility after the shots.