In addition, antibodies can trap (immobilize) individual sperm in mucus gel by forming weak but polyvalent crosslinks between the sperm and the gel-forming mucin fibers. isolated by Shinzo Isojima from the blood of an infertile woman, recognizes a carbohydrate epitope on CD52g, a glycosylphosphatidylinositol-anchored glycoprotein found in abundance on the surface of human sperm. We engineered the antibody for production inNicotiana; the new antibody which we call human contraception antibody, effectively agglutinates sperm at concentrations >10 g/ml and maintains activity under a variety of physiological conditions. We are currently seeking regulatory approval for a Phase 1 clinical trial, VPS33B which will include safety and proof of principle efficacy endpoints. Concurrently, we are working with new antibody production platforms to bring the costs down, innovative antibody designs that may produce more effective second-generation antibodies, and delivery systems to provide extended protection. Keywords:Sperm, monoclonal Hydroxyfasudil antibody, multipurpose prevention technology, contraception, sexually transmitted infections We are engineering monoclonal antibodies and delivery systems for multipurpose prevention technology products that will concurrently prevent sexually transmitted infections and unplanned pregnancies, addressing an important unmet need in reproductive health. For over 10 years, our research team has been working on Hydroxyfasudil monoclonal antibody (mAb)-based multipurpose prevention technology (MPT) products to protect women against sexually transmitted infections (STIs) while at the same time providing contraception to prevent unplanned pregnancies. As STIs are highly prevalent [1], and over 40% of pregnancies worldwide are unplanned [2], MPTs could fill a critical gap. Recent surveys indicate that a large number of women around the world would choose to use an MPT product if available [35]. Since antibodies naturally occur in blood and genital secretions to provide protection [6], human antibody-based MPT products that fortify this natural barrier should pose low risk. Our first product, MB66, is a vaginal film that contains mAbs directed against two incurable sexually transmitted viruses, HIV-1 (VRC01) and herpes simplex viruses 1 and 2 (HSV8). Preclinical studies indicate that the antibodies in MB66 remain active under low pH genital tract conditions and effectively prevent macaques from vaginal SHIV transmission [7]. MB66 was recently tested in a Phase 1 clinical trial and single and multiple dose applications proved to be safe; furthermore, both the HIV and HSV antibodies retained neutralizing activity in vaginal secretions for at least 24 h after film application [8]. We now seek to add an antisperm mAb to MB66 to provide a contraception option for women. In this review article, we discuss: (1) naturally occurring and manufactured antibodies that target and reduce the fertility potential of human sperm; (2) various functions of antisperm antibodies that can affect fertility; (3) selection and manufacture of an antisperm mAb candidate (human contraceptive antibodyHCA); (4) engineering antisperm mAbs with enhanced function; and (5) contraceptive mAb delivery systems. == Antisperm antibodies == Throughout the 20th century, there was considerable interest in naturally occurring antisperm antibodies found in the blood and genital secretions of a sizeable Hydroxyfasudil percentage of men and women with unexplained infertility. Sperm can induce an immune reaction in men after vasectomy or other events that affect the patency of the male Hydroxyfasudil tract, and in some women that, for unknown reasons, are not tolerant to their partners sperm [9]. Antisperm antibodies are detected clinically by assays that assess sperm agglutination, complement-mediated sperm cytotoxicity, or binding of antibodies to the sperm surface (immunobead assay), and were a routine aspect of the assessment of infertile couples [10]. Antisperm antibodies were detected in as many as 15% of couples with unexplained infertility [11]. Many scientists surmised that antisperm antibodies caused infertility, and developed antisperm mAbs to use as tools to identify antigens on the sperm surface that could be targeted for immunocontraception [12] (Table 1). We selected an IgM antisperm mAb, H6-3C4, originally isolated by Isojima et al. [13] from blood cells.
In addition, antibodies can trap (immobilize) individual sperm in mucus gel by forming weak but polyvalent crosslinks between the sperm and the gel-forming mucin fibers
