[Medscape]Anti-sperm antibody contraceptive method trial in sheep.


The researchers report that sperm-binding antibodies could be an effective non-hormonal method of contraception, at least according to early studies in sheep.

According to a report in Science Translational Medicine, when researchers inserted already-generated human anti-sperm antibodies into the vaginas of female sheep, they found a 99.9 reduction in the amount of sperm that migrated forwards. %. Antibodies pull sperm into clumps (a process called agglutination), trapping them in uterine mucus and preventing them from reaching the egg.

According to the Guttacher Institute, more than 10 million women in the United States take birth control pills, but not all of these women are able to use hormonal birth control methods based on hormones. The in vivo experimental evidence described in this new study is a step towards the development of non-hormonal contraceptives for women.

Senior author Samuel Lai, PhD, Professor in the Department of Pharmaceutical Engineering and Molecular Pharmacy at the University of Carolina at Chapel Hill (UNC), told Medscape Medical News, “The potential for using antibodies to prevent pregnancy is known. coming for decades. Initially, researchers focused on developing a birth control vaccine, partly due to the high cost of producing antibodies. However, those approaches largely fail because the altered antibody response can rapidly wane over time, as well as poor control over recovery.”

However, new technology has sparked interest in sperm-based contraception. Lai notes that “great advances in bioremediation have significantly reduced the cost of antibody production, and also advances in molecular biology have allowed us to find antibodies with high potency.”

In a new study, first author Bhawana Shrestha, PhD, a postdoctoral researcher on UNC, and colleagues put together six, eight, or ten antigen-binding fragments to an antibody.” origin”. These antibodies target a small glycoprotein (CD52) found only in human and chimpanzee sperm. The resulting polyvalent antibodies are at least 10 times more potent and able to bind to sperm than unmodified IgG.

In an initial series of experiments, the investigators used computer-aided sperm analysis to show that the three antibodies produced agglutinated sperm in less than a minute – Speed ​​is of the utmost importance in creating an effective contraceptive that stops the journey to the cervix. The “sperm release assay” then evaluates antibodies bound to different sperm densities and to ejaculate or natural sperm that have been washed, absorbed, or subjected to a “high-velocity vortex” to simulate simulate “vaginal agitation and mechanical resistance”.

For the in vivo experiment, his researchers adapted a test that, after digitally used in human clinical trials, can now be tested in sheep, the gold standard of Animal samples are vaginal evaluation. Five sheep received human antibodies and were then stimulated with a vaginal dilator before and after the introduction of whole human semen. A control sheep received unmodified IgG. After 2 minutes, the researchers collected material from the vagina and assessed the sperm’s motility.

Two of the engineered antibodies slowed sperm by more than 97%. Lai says the most effective triad, slowing them down by more than 99%, is being developed in preclinical studies that support IND. The parent IgG on which the new antibodies are based has been in a phase 1a clinical trial, funded by ZabBio Inc. In that trial, 15 women with surgical sterilization were tested for “human contraceptive antibodies” in the form of a vaginal membrane inserted before intercourse. The post-coital test is effective.

According to the author, an intravaginal IUD inserted during monthly childbearing is another possible approach to antibody-based female contraception. Both approaches are likely safe because vaginal normal IgG and antibodies both target a single peptide, sperm.

Erwin Goldberg, PhD, Distinguished Professor of Molecular Sciences at Northwestern University, Evanston, Illinois, who has pioneered the use of anti-sperm antibodies as a contraceptive for women “The current technology can be likened to passive immunity, with local delivery and with more powerful antibodies developed in the laboratory,” she said.

“I don’t think safety is an issue, and in the author’s estimation, the chances of getting pregnant are zero. Overall, the technology is promising and meets the desired goal, but more work is needed,” Goldberg told Medscape Medical News.

One limitation of the study is that it did not assess the ability to prevent pregnancy. A small percentage of sperm can pass through the cervix, Goldberg explains, so further experiments are needed to expand the analysis into the female reproductive tract.

Lai is the director and CEO of Mucommune, a startup developing products for women’s reproductive health, and a director with the CSO of Inhalon, a publicly licensed clinical stage company. muco-trapping antibody technology. Mucommune is partnering with ZabBio Inc in the phase 1a clinical trial mentioned above. Goldberg reports no related financial relationships.

Source: https://www.medscape.com/viewarticle/956627

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Translated by: Thuy Linh

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