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.

Project Start
1988-02-01
Project End
1991-01-31
Budget Start
1988-02-01
Budget End
1989-01-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Reddi, P P; Naaby-Hansen, S; Aguolnik, I et al. (1995) Complementary deoxyribonucleic acid cloning and characterization of mSP-10: the mouse homologue of human acrosomal protein SP-10. Biol Reprod 53:873-81
Reddi, P P; Castillo, J R; Klotz, K et al. (1994) Production in Escherichia coli, purification and immunogenicity of acrosomal protein SP-10, a candidate contraceptive vaccine. Gene 147:189-95
Foster, J A; Klotz, K L; Flickinger, C J et al. (1994) Human SP-10: acrosomal distribution, processing, and fate after the acrosome reaction. Biol Reprod 51:1222-31
Freemerman, A J; Wright, R M; Flickinger, C J et al. (1994) Tissue specificity of the acrosomal protein SP-10: a contraceptive vaccine candidate molecule. Biol Reprod 50:615-21
Kurth, B E; Wright, R M; Flickinger, C J et al. (1993) Stage-specific detection of mRNA for the sperm antigen SP-10 in human testes. Anat Rec 236:619-25
Wright, R M; Suri, A K; Kornreich, B et al. (1993) Cloning and characterization of the gene coding for the human acrosomal protein SP-10. Biol Reprod 49:316-25
Freemerman, A J; Wright, R M; Flickinger, C J et al. (1993) Cloning and sequencing of baboon and cynomolgus monkey intra-acrosomal protein SP-10: homology with human SP-10 and a mouse sperm antigen (MSA-63). Mol Reprod Dev 34:140-8
Shen, M; Wright, R M; Carta, G et al. (1993) Assay for recombinant and native human intraacrosomal antigen SP-10. Am J Reprod Immunol 29:231-40
Beecher, K L; Homyk, M; Lee, C G et al. (1993) Evidence that 68-kilodalton and 54-51-kilodalton polypeptides are components of the human sperm fibrous sheath. Biol Reprod 48:154-64
Homyk, M; Herr, J C (1992) Light and electron microscopic immunolocalization of sperm proteins identified by monoclonal antibodies from the World Health Organization Task Force on Sperm Antigens. J Reprod Immunol 22:237-56

Showing the most recent 10 out of 18 publications