Evaluation of fusogenic trophoblast surface epitopes as targets for immune contraception

• Published in: Contraception (Stoneham) Vol. 71; no. 4; pp. 282 - 293
• Main Authors: Frank, Hans-George, Bose, Patrick, Albieri-Borges, Andrea, Borges, Marcus, Greindl, Alexandra, Neulen, Josepf, Pötgens, Andy J.G., Kaufmann, Peter
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2005; Elsevier Science
• Subjects: Amino Acid Sequence; Anti-implantation strategies; aPL antibodies; Autoantibodies - genetics; Autoantibodies - immunology; Biological and medical sciences; Birth control; Contraception; Contraception, Immunologic; Embryo Implantation; Epitopes - immunology; Female; Genital system. Reproduction; Gynecology. Andrology. Obstetrics; Hormonal contraception; Humans; IVF failure; Medical sciences; Molecular Sequence Data; Peptide mimics; Pharmacology. Drug treatments; Pregnancy; Receptors, Cell Surface - immunology; Recombinant Fusion Proteins - immunology; Sequence Alignment; Trophoblast antibodies; Trophoblast fusion; Trophoblasts - immunology; Anti-implantation strategies; IVF failure; aPL antibodies; Peptide mimics; Trophoblast antibodies; Trophoblast fusion; Trophoblaste; Antigenic determinant; Antibody; Autoantibody; Phospholipid; Implantation; Contraception; Cell fusion; Syncytium; Target
• ISSN: 0010-7824; 1879-0518
• DOI: 10.1016/j.contraception.2004.12.022

Syncytial trophoblast fusion is an essential step in the process of implantation. This project is aimed at the immunological inhibition of syncytial trophoblast fusion as a novel approach to contraception. Fusion-inhibiting recombinant antibodies were generated and used together with autoantibodies from patients with repetitive in vitro fertilization (IVF) failure that were shown to inhibit syncytial fusion and are expected to inhibit implantation, to generate anti-idiotypic peptides. These peptides mimic trophoblast epitopes essential for syncytial fusion and are, therefore, considered specific immunogens for the generation of antibodies that will inhibit implantation. To verify their physiological role in humans, 300 anti-idiotypic peptides were tested for their binding capacity to patient autoantibodies associated with repetitive IVF failure, habitual abortion and preeclampsia. Of these, only three peptides were found to selectively bind to autoantibodies of patients with repetitive IVF failure and were considered safe and efficient enough for evaluation in preclinical and clinical studies required for the development of immune contraceptives. When used as immunogens, these peptides are expected to elicit an antibody response inhibiting syncytial fusion and thus implantation. Furthermore, the action of these antibodies needs to be restricted to the stage of syncytium formation at the time of implantation so as not to cause complications of pregnancy in those cases where they fail to have a contraceptive effect. To exclude potential side effects on other systems, toxicological experiments in animals are in progress.