The overall goal of this research program is to develop a contraceptive vaccine for women by isolating and testing one or several human sperm membrane immunogens. The immediate research aims are directed toward purifying sufficient quantities of specific immunogen to formulate a vaccine and test its immunogenicity in a small animal and a primate model after identifying species whose sperm share the immunogen with human sperm. A target immunogen termed the MHS-10 antigen, which localizes over the acrosomal cap, has been selected for development. This immmunogen was identified as a primary vaccine candidate by the WHO Task Force on Vaccines for Fertility Regulation. The MHS-10 immunogen will be characterized with regard to tissue specificity, incidence in the human population, and cross reactivity with other species. The immunogen will be purified by affinity chromatography and characterized biochemically, including amino acid and carbohydrate composition, and amino terminal amino acid sequence data. An oligonucleotide(s) complementary to the mRNA encoding the amino terminis of the MHS-10 immunogen will be synthesized. The genes coding the MHS-10 immunogen will be cloned in lambda gt11 and the immunogen will be produced in an expression system. Immunocytochemical studies at light and EM levels will explore the cellular and subcellular localization of the immunogen during spermatogenesis and sperm maturation. Sufficient quantities of the immunogen will be obtained through preparative biochemistry and/or bacterial expression to formulate and test the immunogenicity of a first generation vaccine. It is anticipated that this research program will provide fundamental information regarding the molecular architecture of a molecule found in the plasma membrane overlying the human sperm acrosome, including its amino acid sequence, encoding gene and its development during spermatogenesis. In addition, the capacity of this molecule to elicit an immune response and antifertility effects will be investigated, potentially leading to development of a novel contraceptive vaccine.
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