The long term goals of this research project are to continue to address the problem of prefertilization immunocontraception from the perspective of a defined mammalian sperm surface component and its role in achieving contraception by the antigen's specific antibody interfering with fertilization. It is our goal to define at the molecular and physiological level a set of sperm molecules which functions during fertilization and whose primary sequences can be engineered into an effective immunocontraceptive. Hence, a blending of molecular biology and sperm physiology will lead us to a better understanding of precise targets for contraception. To continue this line of inquiry, the current proposals's specific aims are directed toward studies on the effect on fertility of mice and monkeys immunized with constructs derived from human Sp17 (rHSp17), and a combination of rHSp17 and zona pellucida (ZP) constructs.
Aim number 1: Fertility testing in mice and immunogenicity testing in monkeys of chimeric peptides consisting of a promiscuous T-cell epitope and a rHSp17 peptide synthesized as a single synthetic peptide.
Aim number 2: Fertility testing in mice and immunogenicity testing in monkeys of recombinant proteins which represent portions of the entire HSp17 sequence that contain specific immunodominant epitopes and portions of the zona pellucida sequence which represent the sperm binding site(s).
Aim number 3: A fertility trial of 15 immunized monkeys and 15 control monkeys.
Aim number 4: the physiological characterization of human Sp17 by examining in detail its expression in a eukaryotic cell.
Aim number 5: An examination of the effect on fertility in mice immunized with two different recombinant proteins from sperm and zona pellucida.
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