Currently, most available birth control options are barrier methods or rely on hormones to prevent fertilization of an egg—both of which have drawbacks, such as discomfort or side effects, that make them less than ideal for some people. Enter antisperm antibodies, described in a study published today (August 11) in Science Translational Medicine. Researchers generated antibodies that recognize an antigen unique to human sperm. When delivered topically to the reproductive tracts of sheep, the antibodies successfully bound and trapped more than 99.9 percent of introduced human sperm. Some of the authors have spun out a company, Mucommune, in order to continue the development of contraceptives based on these antibodies.
“I’m a strong proponent of using antibody therapeutics in clever ways that benefit people, and I think they’ve latched onto something here,” says Janice Reichert, who directs The Antibody Society, a nonprofit that supports antibody research and development, and was not involved in the study. She explains that most of the hundreds of antibody-based therapies currently in clinical trials are targeted toward molecules involved in cancer or immune-mediated disorders and are delivered intravenously, making the topical and regional applications for contraception proposed in the current study unusual.
It’s not largely appreciated that human bodies secrete as many, if not more, antibodies into mucus as into either blood or lymph, says study coauthor Sam Lai of the University of North Carolina Eshelman School of Pharmacy. About a decade ago, Lai’s group began to investigate the mucus–antibody interaction in an effort to find better ways to protect against infections in the lungs, as well as sexually transmitted infections and unwanted pregnancies.
Previous work showed that some women’s bodies naturally produce antibodies to sperm that can lead to a type of immunological infertility. Lai’s group used the antigen binding fragment from one of these antibodies, which recognizes a sperm-specific antigen known as CD52g, in a study published in 2020, where they engineered an IgG antibody with four of the antigen-binding fragments and showed that it and the original, naturally-occurring IgG antibody with two antigen binding domains trapped sperm in vitro.
In the new study, Lai and colleagues added multiple antigen-binding fragments—6, 8, or 10—to an IgG antibody and then introduced expression plasmids into human embryonic kidney cells so the cells would produce them and researchers could isolate them. The team tested the antibodies’ ability to immobilize sperm in vitro, where the antibodies with extra antigen-binding fragments trapped sperm at least 10 times more effectively than the original IgG antibody with just two antigen-binding fragments.
To explore the effects of the antibodies in vivo, the researchers introduced the original IgG antibody, one with 6 or 10 antigen-binding fragments, or saline into the vaginas of female sheep, which are similar to the human female reproductive tract, and then simulated intercourse and delivered a human semen sample. Two minutes later, they retrieved the sample and analyzed sperm movement. At a high dose (333 micrograms of antibody), all three antibodies tamped down nearly all sperm motility, and at a low dose (33.3 micrograms), both modified antibodies, but not the original IgG, trapped more than 90 percent of sperm.
“It’s a lot of impressive work and a really interesting idea,” says Pascal Gagneux, an evolutionary biologist at the University of California, San Diego, who was not involved in the study. Some of the open questions, according to Gagneux, are how similar sheep and human vaginal mucus are and how successful the antibody will be at preventing pregnancy. “This thing better be really, really airtight, because even if it’s surprising how many sperm get incapacitated, as long as you have one, you could still theoretically get pregnant,” he says.
Lai agrees that the next step is to move into the clinic. Through their company Mucommune, the team is currently working on incorporating the antibodies into a vaginal film or ring that could be used during fertile periods to prevent pregnancy. “In the long run, we would also be interested in exploring other methods of delivery [such as injectables] that would satisfy the needs of different subgroups of women,” he says.
Coauthor Bhawana Shrestha, a former grad student and now postdoc in the Lai lab, says she was drawn to the project based on “the limitations of existing contraception.” People think the need for nonhormonal contraception is already met via intrauterine devices and other products, she adds, “but that is so far from the truth.”