Anti-sperm antibodies tested as contraceptives in sheep

Antibodies that bind to semen could be an effective non-hormonal method of birth control, at least according to early studies in sheep, the researchers report.

When researchers introduced modified human anti-sperm antibodies into sheep’s vaginas, they found a 99.9% drop in moving sperm, according to a report in Science Translational Medicine. The antibodies cause the sperm to clump together (a process called clumping), trapping them in the cervical mucus and preventing them from reaching the egg.

More than 10 million women in the United States take birth control pills, according to the Guttmacher Institute, but not all women can use hormone-based contraceptives. The in vivo proof of concept experiments described in the new study are a step towards the development of a contraceptive for women.

“The possibility of exploiting antibodies for contraception has been known for decades. Initially, researchers focused on developing contraceptive vaccines, in part because of the exorbitant costs of manufacturing antibodies. However, these approaches have largely failed due to the variable antibody response which can rapidly decline over time, as well as poor control of reversibility, ”said lead author Samuel Lai, PhD, professor in the Division of pharmacoengineering and molecular pharmacology from the University of North Carolina at Chapel Hill (UNC). Medscape Medical News.

However, new technologies have revived interest in semen-based contraception. Lai credits “the remarkable advancements in bioprocessing that have dramatically reduced the cost of manufacturing antibodies, as well as advances in molecular biology that allow us to design antibodies with greater potency.”

In the new study, first author Bhawana Shrestha, PhD, a postdoctoral researcher at UNC, and his colleagues attached six, eight or 10 antigen-binding fragments to a “parent” IgG antibody. The antibodies target a small glycoprotein (CD52) found only in human and chimpanzee sperm. The modified multivalent antibodies have a potency and sperm binding capacities at least 10 times that of unmodified IgGs.

In a first set of experiments, the researchers used computer-assisted sperm analysis to show that the three modified antibodies agglutinated sperm in less than a minute – speed is important for designing a contraceptive that effectively blocks the journey. up to the cervix. Next, “sperm escape tests” evaluated the antibodies with different sperm densities and with sperm or native sperm that had been washed, capacitated or subjected to a “high speed vortex” to simulate “agitation. and mechanical stress in the vagina ”.

For the in vivo experiments, the researchers adapted a post-coital test used in human clinical trials to test in sheep, the reference animal model for the evaluation of vaginal products. Five sheep received the modified human antibodies and were then stimulated with a vaginal dilator before and after administration of whole human sperm. A control sheep received unmodified IgG. After 2 minutes, the researchers collected material from the sheep’s vagina and assessed the motility of the sperm.

Two of the modified antibodies slowed down sperm by over 97%. The most effective of the trio, which slowed them down by over 99%, is being developed in preclinical studies allowing IND, said Lai. The parent IgG on which the new antibodies are based is already in a phase 1a clinical trial, sponsored by ZabBio Inc. In this trial, 15 surgically sterilized women test for “human contraceptive antibody” in the form of a vaginal film inserted before intercourse. Postcoital tests evaluate the effectiveness. (The authors of the new article have financial ties to ZabBio.)

An intravaginal ring inserted during the monthly fertility window is another possible method of administration for an antibody-based female contraceptive, according to the authors. Either approach is probably safe because IgG is a normal resident of the vagina and the antibodies target a peptide unique to semen.

“The current technology can be compared to passive immunization, with local administration and with more potent antibodies designed in the laboratory,” said Erwin Goldberg, PhD, professor emeritus of molecular biosciences at Northwestern University, Evanston, Illinois, who has did pioneering work on the use of anti-sperm antibodies as a female contraceptive.

“I don’t think safety is an issue, and according to the authors’ estimates the chances of pregnancy are slim to zero. Overall, the technology is promising and the goal is desirable, but more work is needed. necessary, ”Goldberg said. Medscape Medical News.

One limitation of the study is that it did not assess prevention of pregnancy. A small percentage of sperm pass the cervix, Goldberg explained, so more experiments are needed to expand the analysis into the female reproductive system.

Lai is the founder and CEO of Mucommune, a start-up that develops products for female reproductive health, and is the founder and CSO of Inhalon, a clinical stage company that has licensed mucomucosal scavenging antibody technologies. Mucommune is collaborating with ZabBio Inc on the phase 1 clinical trial mentioned above. Goldberg did not report any relevant financial relationship.

Sci Transl Med. Published online August 11, 2021. Abstract

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