Male vaccine studied; shot not yet a reality

"Thanks to one biotech company, the promise of a Pill-style prophylactic for men may finally take off," proclaims a popular men’s magazine article.1 For those involved in such research, however, that promise is not yet a product.

Even the most favorable experimental male contraceptives are at least a decade away from general use, according to a 1998 review of methods under research.2 Progress has been slow in part due to the challenge of controlling the male reproductive system. While a woman produces one egg a month, a man generates hundreds of millions of sperm daily. And while a woman’s fertility ends at menopause, a man continues to produce sperm throughout his adult life.

Scientists are looking at a variety of hormonal and nonhormonal approaches to suppress sperm production, but the process in question pertains to the inhibition of the sperm’s fertilizing ability. (Contraceptive Technology Update offered a review of methods under research in its February 1998 issue; see p. 22.)

Immucon, a Montreal, Quebec-based firm, has filed a U.S. patent based on its claim that it can use a fragment of a protein to neutralize the sperm’s fertilizing capacity acquired at the level of the epididymis.

In tests on rodents, scientists affiliated with Immucon have found that the protein P26h is responsible for informing sperm cells when they have reached the surface of an egg.3 This protein is very important for the binding to the ovum, says Alain Bossé, Immucon president. If it is not there or if its action is blocked by immunocontraception, fertilization does not occur, he explains. "What we have done is to take a segment of this protein and inject it into the hamster’s body, and antibodies are developed against this P26h" he says. "They bind themselves to the sperm head, and when the sperm goes out, it cannot fertilize."

Immucon researchers have identified P34H in humans as the target protein.4 Clinical trials will have to be conducted to determine whether the principle holds true in men. "We are about to begin the monkey studies," says Bossé. "We hope to be in Phase I studies about two to 2½ years from now."

Immucon, which maintains its own Web site (www.immucon.com), has received much interest from men seeking the experimental method, says Bossé. "Everybody is asking [about the contraceptive method] and telling about their personal case, about their partner is having trouble with female contraceptives."

The need for that market isn’t being met, he says. "People are asking if they can’t have it now, then they are willing to use it in clinical trials."

Paul Primakoff, PhD, professor in the department of cell biology at the School of Medicine at University of California-Davis Medical School, and members of his research team have identified and studied other proteins on the surface of sperm that are required for fertilization. One protein, identified as PH-20, helps a sperm cell penetrate the outer layer of cells that surrounds the egg. It also appears to help a sperm cell adhere to the egg coat, which lies between the cumulus cell layer and the egg cell membrane. Another protein, identified as PH-30 or fertilin, is required for a sperm cell to bind and fuse to the egg cell membrane.

In rodent studies, UC-Davis researchers have found the proteins to be extremely effective contraceptive vaccines. When they inject preparations of one or both proteins into rodents, the animals respond by synthesizing antibodies specific to the proteins. The antibodies then bind to the proteins as they appear on the surface of sperm cells. Thus, they prevent the proteins from participating in the events of fertilization.

Creating infertility

Taking their research a step further, scientists studied the activity of sperm in mice lacking the gene for fertilin-beta.5 Sperm from the mutant mice looked and moved normally, but most of them failed to attach to the egg. Those sperm fused with the plasma membrane, which encases the egg, at just half the rate of sperm from normal mice.

"That is another kind of proof of concept that if you can delete the activity of a single sperm protein, then you can create this infertility," observes Primakoff. "Then the question becomes, When you want to make this into a contraceptive method, how do you delete this protein? Can you really do it with antibodies, or are there possible approaches through a pharmaceutical?’"

Primakoff says he is often questioned on a possible timetable for contraceptive products, but he says it is too early to make any predictions. "Being involved in it, and seeing how the science goes, it is really hard to say, but I don’t believe it is close," he remarks. "I don’t think anyone has really figured out how to do this."

References

1. Murphy M. Emission control. Esquire, October 1999: 167-169.

2. Best K. Experimental male methods inhibit sperm. Network 1998; 18:16-19, 31.

3. Berube B, Sullivan R. Inhibition of in vivo fertilization by active immunization of male hamsters against a 26-kDa sperm glycoprotein. Biol Reprod 1994; 51:1,255-1,263.

4. Boue F, Berube B, De Lamirande E, et al. Human sperm-zona pellucida interaction is inhibited by an antiserum against a hamster sperm protein. Biol Reprod 1994; 51:577-587.

5. Cho C, Bunch DO, Faure JE, et al. Fertilization defects in sperm from mice lacking fertilin beta. Science 1998; 281:1,857-1,859.