Immunobiological Role of Fertilization Antigen(FA-1)

West Virginia University, Morgantown WV

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Fertilization antigen (FA-1) is a testis/sperm-specific glycoprotein that is present on sperm of various mammalian species including man and mouse and has a role in fertilization. It is involved in human immunoinfertility and the recent clinical trial indicates that it may have clinical applications in specific diagnosis and treatment of immunoinfertile men. The cDNAs encoding for murine and human FA-1 antigens have been cloned and sequenced. Active immunization of female mice with murine recombinant(r) FA-1 antigen or with another recently identified novel sperm-specific dodecamer synthetic peptide, designated as YLP12, causes an overall 70% reduction, rather than a complete block, of fertility with either vaccine, due to inter-individual variability of the immune response. The present proposal has four specific aims and will focus on obtaining FA-l-reactive human monoclonal antibodies that could be used as a passive immunocontraceptive to avoid variability of the immune response, and on testing the bivalent vaccine having FA-1 antigen and YLP12 together in a single formulation to obtain a complete block in actively immunized female mice. Specific aim 1 is to construct a combinatorial phage display library having y1 heavy (H) and kappa light (L) chains cDNA inserts of Fab antibodies, reverse-transcribed from RNA isolated from peripheral lymphocytes of immunoinfertile men. Specific aim 2 is to select the human rFA-1 antigen-reactive clones from the library using the panning procedure and sequence the Hand L-chain inserts of the selected clones. Specific aim 3 is to investigate the immunobiological effects of the Fab antibodies secreted by the human rFA-1 antigen-reactive clones by using various assays. Specific aim 4 is to investigate the immunocontraceptive effect of the bivalent vaccine, having murine rFA-1 antigen and synthetic YLP12 peptide in a single formulation, in actively immunized female mice. Besides enabling us to study the structure-function relationship, these studies will examine the utility of recombinant FA-1 antigen and synthetic YLP12 peptide, and recombinant human antibodies in immunocontraception and immunoinfertility in humans. [unreadable] [unreadable]