Mary Carol
17-11-04, 09:09 AM
Blocks Male Fertility In Monkeys
Jennifer Couzin
When the 1880s debut of vulcanized rubber and the 1930s advent of latex mark the latest advances, one quickly understands the sorry state of male contraceptives. Researchers in this beleaguered field have tried to supply men with other options but have had little success. Now, on page 1189 of this issue of Science, a team in the United States and India reports preliminary results of its new contraceptive vaccine for males. Although not without problems, the vaccine prevented pregnancy in female partners of the male monkeys receiving it.
"There seems to be some real promise," says Ronald Swerdloff, a reproductive endocrinologist at the University of California, Los Angeles. Still, "it's just early in the game," with too few monkeys tested, to conclude whether the approach will pan out, he adds.
Reproductive biologist Michael O'Rand of the University of North Carolina, Chapel Hill, crafted the vaccine several years after reporting his discovery of a novel male-only protein in 2001. The protein, called Eppin, has been found so far on the surface of sperm cells and elsewhere in the testis and the epididymis. Its function isn't clear. But drawing on the general strategy of immunocontraception, in which vaccines are designed to act as contraceptives, O'Rand reasoned that if a male harbored antibodies to this protein, his sperm might malfunction.
O'Rand teamed up with colleagues at the Indian Institute of Science in Bangalore, which hosts a large primate research center. There, the group vaccinated six monkeys with human recombinant Eppin protein and administered a sham vaccine to six others. The team hypothesized that the monkeys needed high levels of antibodies to Eppin in their blood for the vaccine to work, especially because antibody levels drop in the epididymal fluid. So when only four of the six treated monkeys displayed antibody levels that O'Rand's team deemed sufficient, the other two animals were dropped from the study. The team brought in three additional monkeys, who also reached the desired antibody levels. It's not clear why some monkeys did not produce sufficient antibodies, a problem other immunocontraceptives have encountered.
The monkeys received boosters of vaccine every 3 weeks. Because the vaccine didn't lower sperm count or alter sperm in an easily detectable way, scientists resorted to another method of testing its effectiveness: The immunized male monkeys spent several days each with three different females during the fertile peak of the females' menstrual cycle. The upshot: None of the seven vaccinated monkeys managed to impregnate a female. Four of the six control monkeys did.
The contraceptive effect of the vaccine was intended to be reversible; once the booster shots were stopped, the researchers anticipated that antibodies to Eppin would decline and fertility would return. But only five of the seven vaccinated monkeys, some of whom received booster shots for nearly 2 years, recovered their fertility during the course of the study. "It's hard to say" what that means, says O'Rand. "Maybe they recovered 2 weeks after we quit" testing them. Although conceding that the vaccine has a long way to go, O'Rand believes the study offers "a proof of principle" for immunocontraception, which has been so relegated to the sidelines that the National Institutes of Health no longer funds research on it.
Companies have also been hesitant. New Jersey-based Organon studied immunocontraception for females before backing out, says Willem de Laat, the company's medical director. Instead, Organon and another company, Schering in Berlin, are testing a combination of oral progestin and injected testosterone.
O'Rand and his colleagues, heartened by what they consider a success, are now trying to understand how, exactly, their vaccine disrupts fertility. One possibility is that the technique leaves sperm sluggish. Whatever its mechanism, O'Rand and other contraceptive researchers hope the new vaccine will provide a shot in the arm for the field.
Science Magazine
Volume 306, Number 5699, Issue of 12 Nov 2004, p. 1117.
Jennifer Couzin
When the 1880s debut of vulcanized rubber and the 1930s advent of latex mark the latest advances, one quickly understands the sorry state of male contraceptives. Researchers in this beleaguered field have tried to supply men with other options but have had little success. Now, on page 1189 of this issue of Science, a team in the United States and India reports preliminary results of its new contraceptive vaccine for males. Although not without problems, the vaccine prevented pregnancy in female partners of the male monkeys receiving it.
"There seems to be some real promise," says Ronald Swerdloff, a reproductive endocrinologist at the University of California, Los Angeles. Still, "it's just early in the game," with too few monkeys tested, to conclude whether the approach will pan out, he adds.
Reproductive biologist Michael O'Rand of the University of North Carolina, Chapel Hill, crafted the vaccine several years after reporting his discovery of a novel male-only protein in 2001. The protein, called Eppin, has been found so far on the surface of sperm cells and elsewhere in the testis and the epididymis. Its function isn't clear. But drawing on the general strategy of immunocontraception, in which vaccines are designed to act as contraceptives, O'Rand reasoned that if a male harbored antibodies to this protein, his sperm might malfunction.
O'Rand teamed up with colleagues at the Indian Institute of Science in Bangalore, which hosts a large primate research center. There, the group vaccinated six monkeys with human recombinant Eppin protein and administered a sham vaccine to six others. The team hypothesized that the monkeys needed high levels of antibodies to Eppin in their blood for the vaccine to work, especially because antibody levels drop in the epididymal fluid. So when only four of the six treated monkeys displayed antibody levels that O'Rand's team deemed sufficient, the other two animals were dropped from the study. The team brought in three additional monkeys, who also reached the desired antibody levels. It's not clear why some monkeys did not produce sufficient antibodies, a problem other immunocontraceptives have encountered.
The monkeys received boosters of vaccine every 3 weeks. Because the vaccine didn't lower sperm count or alter sperm in an easily detectable way, scientists resorted to another method of testing its effectiveness: The immunized male monkeys spent several days each with three different females during the fertile peak of the females' menstrual cycle. The upshot: None of the seven vaccinated monkeys managed to impregnate a female. Four of the six control monkeys did.
The contraceptive effect of the vaccine was intended to be reversible; once the booster shots were stopped, the researchers anticipated that antibodies to Eppin would decline and fertility would return. But only five of the seven vaccinated monkeys, some of whom received booster shots for nearly 2 years, recovered their fertility during the course of the study. "It's hard to say" what that means, says O'Rand. "Maybe they recovered 2 weeks after we quit" testing them. Although conceding that the vaccine has a long way to go, O'Rand believes the study offers "a proof of principle" for immunocontraception, which has been so relegated to the sidelines that the National Institutes of Health no longer funds research on it.
Companies have also been hesitant. New Jersey-based Organon studied immunocontraception for females before backing out, says Willem de Laat, the company's medical director. Instead, Organon and another company, Schering in Berlin, are testing a combination of oral progestin and injected testosterone.
O'Rand and his colleagues, heartened by what they consider a success, are now trying to understand how, exactly, their vaccine disrupts fertility. One possibility is that the technique leaves sperm sluggish. Whatever its mechanism, O'Rand and other contraceptive researchers hope the new vaccine will provide a shot in the arm for the field.
Science Magazine
Volume 306, Number 5699, Issue of 12 Nov 2004, p. 1117.