Archive for Monday, July 25, 2005

Birth-control vaccine shows promise in animals

July 25, 2005

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— Imagine a temporary immunity to baby-making.

A University of Missouri at Columbia researcher is aiming for the ultimate female contraceptive: a vaccine that would make sperm bounce off eggs like they were brick walls.

"You almost have it in the back of your head that this is too good to be true," said MU animal scientist Peter Sutovsky, who can block fertilization 100 percent of the time when he puts certain antibodies in a petri dish of pig eggs and sperm. Antibodies are the immune system's natural way of fighting what it thinks is foreign and dangerous.

Sutovsky acknowledges that the next step - making a safe vaccine that provokes the body to produce the antibodies itself - has meant failure for many other scientists tantalized by the idea of a hormone-free immunocontraceptive.

But his work could spark an otherwise stagnant industry. The last revolution in male contraception was in the 1930s, when latex condoms became available. The hormonal concept of the pill hasn't changed since it was first tested in 1955. Meanwhile, there are millions of unintended pregnancies in the United States, and hundreds of millions worldwide.

"It tells you we've undermet the need for contraception," said Lawrence Finer, a research director at the New York-based Guttmacher Institute, which studies reproductive health and policy.

Preventing conception

Sutovsky wants to meet that need with a contraceptive that would work in the moment just before conception.

When sperm bind to the outer edge of the egg wall, a cap in their heads bursts open, releasing proteasomes. Proteasomes are cellular garbage collectors; they eat proteins that are "tagged" as old or broken.

Sutovsky discovered that the egg wall is tagged just like a broken protein. The sperm proteasomes attack it, and create a tunnel. When Sutovsky blocked the proteasomes with antibodies, sperm couldn't burrow through to the egg. He's currently vaccinating mice, hoping that mice can produce the antibodies themselves.

Rajesh Naz isn't holding his breath. "Almost half a century has passed and there's nothing new in contraception," said the West Virginia University reproductive immunologist, who is working on his own contraceptive vaccines. He says a good one is at least five to 10 years away.

Vaccines are tricky, Naz said. Even well-established vaccines, like those for measles or tetanus, have a failure rate. Individual immune systems can overreact or underreact. Another problem is getting enough antibodies, which usually patrol the bloodstream, in the mucous membranes where fertilization occurs.

A third worry is side effects, Naz said. Researchers want the antibodies to attack only the sperm or egg. If the target protein exists anywhere else in the body, a contraceptive vaccine would cause the body's immune system to attack itself. Naz says only a handful of unique sperm or egg proteins have been discovered.

Sutovsky says his proteasomes could be unique. The payoff of a viable vaccine could be huge, because hormones in the pill can cause undesirable side effects for some women. The pill carries a risk for cardiovascular disease and stroke, especially for smokers.

The pill also requires the user to remember to take it every day. A vaccine could require only an annual booster shot. Women who want to become fertile again would simply not get a booster, Sutovsky suggests.

Little corporate interest

Despite the promise of immunocontraceptives, pharmaceutical companies are biding their time and sticking with the hormonal approach, says University of North Carolina reproductive biologist Michael O'Rand, who has worked on a male immunocontraceptive.

"They didn't come knocking at my door. They don't see the development of a vaccine or immunization as the way to go," he said.

O'Rand vaccinated seven male monkeys and prevented them from impregnating females, according to a 2004 study published in the journal Science. The vaccine caused the monkeys to make antibodies for eppin, a sperm protein. Without eppin, sperm get stuck in semen and can't swim.

O'Rand has abandoned the vaccine approach and instead is trying to target eppin directly with drugs.

Finer argues that the number of unintended pregnancies means there's a need for a contraceptive that is more effective, cheaper or easier to use. From 1995 to 2000, the world's 1.3 billion women between the ages of 15 and 45 had more than 1.2 billion pregnancies, according to 2002 estimates by the Global Health Council, a Washington-based nonprofit group that studies issues in women's and children's health. One-quarter of those pregnancies - 300 million, or more than the population of the United States - were unintended, the council found.

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