Modified antibody fragment blocks fertilization, paving way for nonhormonal contraceptive

A new study from Karolinska Institutet shows how a small antibody fragment can block fertilization by targeting a key protein on the surface of the egg. This discovery brings a nonhormonal contraceptive one step closer to reality. The study has been published in the Proceedings of the National Academy of Sciences.

In the study, the researchers describe how a modified antibody fragment can block fertilization by targeting the protein ZP2 on the surface of the egg. “Our study shows how a small antibody fragment can block fertilization by targeting ZP2, a key protein in the outer layer of the egg that is involved in both sperm binding and blocking polyspermy,” says Luca Jovine, Professor of Structural Biology at the Department of Medicine, Huddinge (MedH).

The researchers have used X-ray crystallography to map the interaction between the antibody IE-3, which is known to prevent fertilization in mice, and ZP2 at the atomic level. A modified, smaller version of the antibody (scFV) was found to be equally effective, blocking fertilization in 100% of IVF tests with mouse eggs. Because it lacks the immune-triggering Fc region of the full antibody, scFV minimizes potential side effects.

“Despite its small size, the fragment remained effective, reducing potential side effects,” explains Jovine. These findings provide a basis for a targeted, reversible contraceptive method that avoids hormone-related risks.

Current methods of contraception rely on hormones, which can cause side effects such as mood changes, headaches or increased risk of blood clots. Blocking fertilization on the surface of the egg has been proposed as an alternative, but antibodies were deemed unsuitable due to possible immune responses triggered by their Fc region.

The next step in the research is to develop a similar antibody that targets human ZP2 and test whether its scFV fragment can block fertilization in human IVF. If this is successful in IVF experiments, the next phase will focus on assessing safety, stability and potential delivery methods, bringing researchers closer to a nonhormonal contraceptive method for human use.