Contraceptive antibodies are here!

Article source: Medical Rubik's Cube Pro

Author: Li Yuan

Traditional contraceptive methods include physical barriers and hormonal drugs.
These methods have their own advantages and disadvantages.
In particular, hormonal drugs have side effects such as depression, nausea, and migraine
.

In view of the fact that the core of almost all contraceptive methods is to prevent the combination of sperm and eggs, if sperm are regarded as foreign invaders that interfere with normal body function, can the development of contraceptive methods be carried out by capturing sperm antigens?

In fact, the concept of sperm antibodies has not been proposed for the first time.
Previous studies have found that some women's bodies naturally produce sperm antibodies, which can lead to infertility
.
The team of Dr.

In a new study published in Science Translational Medicine on August 11, the research team introduced an antibody that recognizes human sperm-specific antigens that can bind to and capture over 99% of human sperm in the vagina of sheep
.
Researchers also founded a company (Mucommune) to continue the development of such antibody contraceptives

The original IgG antibody has only two antigen-binding fragments.
In this new study, the researchers designed a group of multivalent IgG (HM-IgG) with 6-10 antigen-binding fragments, namely FIF (6-Fab HM).
-IgG), FIFF (8-Fab HM-IgG) and FFIFF (10-FabHM-IgG)
.
These antigen-binding fragments are isolated from sperm antibodies in an immunized infertile woman and can specifically target the CD52g antigen.

Production and characterization of multivalent sperm antibodies (Source: Science Translational Medicine)

The researchers first tested the ability of HM-IgG to immobilize sperm in vitro.
They found that HM-IgG with additional antigen-binding fragments had at least 10 to 16 times higher sperm agglutination efficiency than original IgG with only two antigen-binding fragments, and the speed Faster
.

Multimerization enhances the agglutination efficiency of anti-sperm IgG antibodies (Source: Science Translational Medicine)

Since CD52g is only found in the sperm of humans and chimpanzees, there is currently no practical animal model to conduct mating-based contraceptive studies, and the sheep vagina is very similar in physiology and anatomy to the human vagina, and the researchers designed accordingly A study of sheep
.

The research procedure is to first inject phosphate buffered saline (PBS), IgG, 6-Fab HM-IgG or 10-Fab HM-IgG into the vagina of female sheep, and then carry out simulated mating and vaginal infusion of human semen samples.
Two minutes after the semen instillation, a semen sample was retrieved for analysis of sperm motility
.

The results show that at high doses (333 μg), almost all sperm motility can be effectively inhibited by the three antibodies
.
At low doses (33.

In in vivo studies, multivalent anti-sperm IgG showed stronger agglutination efficiency than original IgG (Source: Science Translational Medicine)

Of course, if this sperm antibody is to be introduced into the clinic, there are still some problems that need to be resolved
.
For example, because this study did not directly prove the effectiveness of antibodies by preventing pregnancy, subsequent research and development also need to determine the success rate of antibodies in this regard, in addition to the similarity between sheep and human vaginal mucus and its influence on the experimental results.

The current focus of the research team is to integrate antibodies into the vaginal membrane or ring for contraception during pregnancy
.
Dr.

Reference materials:

[1] Bhawana S.

[2] Antibodies Stop Sperm in Their Tracks (Source: TheScientist)