The primary goal of this grant is to test the anti-fertility potential of a contraceptive vaccine in female baboons. The principal ingredient in the vaccine is an antigen, termed SP-10, existing on the human and baboon sperm head in association with the acrosomal membranes and recently cloned from the human testis. The vaccine will be a fusion protein construct, containing 248 amino acids of SP-10 linked to 26 kD of glutathione transferase. The vaccine will be injected intramuscularly. Toward this primary goal, an initial aim will be the genetic engineering of the SP-10 polypeptide into the pGex expression vector and the purification by affinity chromatography of pure fusion protein to serve as the immunogen and for various assays. To insure that the exact homology between human and baboon SP-10 is understood, baboon SP-10 will be cloned and sequenced from baboon testis utilizing cDNA libraries which we will construct and screen with a human SP-10 nucleotide probe. Messenger RNA from all major baboon organs will be isolated and probed by Northern blotting with the human SP-10 probe to determine if any baboon organ other than testis expresses mRNAs for SP-10. This dat will re-inforce immunohistochemical and ELISA data already obtained which indicate SP-10 is a tissue specific antigen unlikely to elicit autoimmune reactions. Fertility trials of the vaccine will be conducted in 15 female baboons with 15 females receiving the vaccine ingredients minus the SP-10 immunogen. Following immunization, each baboon will be monitored through 9 menstrual cycles for evidence of conception and for anti-SP-10 antibody responses in serum and cervial mucus. Histopathological examination of baboon organs will be conducted at the conclusion of the study. The baboon serum antibodies to SP-10 will be employed to determine the immunodominant portions of the SP-10 molecule.
The research aims outlined in this proposal follow the direct path to development of a contraceptive vaccine with potential use in human females.
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