The focus of this Center is immunocontraception in which the target is surface molecules of the sperm cell. Immunocontraception directed against the gamete surface is the most sophisticated barrier method of contraception, where the barrier is at the molecular level. Remarkable advances have occurred recently in immunology, molecular biology and fertilization research. These advances have combined to open possibilities for immunocontraception that were previously imagined but unattainable. Project #1 (Primakoff) proposes to develop a birth control vaccine for women which blocks fertilization and is effective, safe and widely acceptable. The vaccine uses the sperm surface protein PH-20, the only sperm protein shown to give 100% effective contraception in female animal model. Project #2 (Myles) proposes two novel strategies for development of male immunocontraceptives. The first strategy uses a vaccine based on a single epitope of the PH-30 protein. This epitope is required in fertilization and is present on epididymal but not testicular sperm. The second strategy, passive immunization, involves sustained release of monoclonal antibodies in the male which recognize either PH-20 or PH-30, sperm proteins required for fertilization. Project #3 (Bigazzi) proposes another comprehensive strategy for a male vaccine. In this case, male mice and monkeys will be immunized with PH-20 or peptides from PH-20. The immunization protocols, adjuvants and peptides will be screened to find those that induce infertility an avoid inflammation in the testis. Project #4 (Bleil) proposes the isolation of a unique type of immunocontraceptive monoclonal antibody (Mab). The Mab will inactivate sperm in the female reproductive trace by inducing a premature acrosome reaction. Project #5 (Saling) is based on Saling's discovery of a sperm plasma membrane tyrosine kinase, p95, that has properties of a receptor for ZP3. Saling proposes to clone cDNAs for mouse and human p95 and test them as contraceptive immunogens in mice and primates. Project #6 (Langer) is focused on a sustained release device for antigens that vies long-term, high titer immunization, the ideal features for a contraceptive vaccine. The further refinement of the polymeric release device developed by Langer and its application to contraceptive vaccines is proposed.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD029125-04
Application #
2201601
Study Section
Special Emphasis Panel (SRC (07))
Project Start
1991-09-30
Project End
1996-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Anatomy/Cell Biology
Type
Schools of Dentistry
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030
Sutton, Keith A; Jungnickel, Melissa K; Ward, Christopher J et al. (2006) Functional characterization of PKDREJ, a male germ cell-restricted polycystin. J Cell Physiol 209:493-500
Yu, Junying; Deng, Manqi; Medvedev, Sergey et al. (2004) Transgenic RNAi-mediated reduction of MSY2 in mouse oocytes results in reduced fertility. Dev Biol 268:195-206
Yu, Junying; Hecht, Norman B; Schultz, Richard M (2003) Requirement for RNA-binding activity of MSY2 for cytoplasmic localization and retention in mouse oocytes. Dev Biol 255:249-62
Talbot, Prudence; Shur, Barry D; Myles, Diana G (2003) Cell adhesion and fertilization: steps in oocyte transport, sperm-zona pellucida interactions, and sperm-egg fusion. Biol Reprod 68:1-9
Miller, Christopher J; Lu, Fabien X (2003) Anti-HIV and -SIV immunity in the vagina. Int Rev Immunol 22:65-76
Tollner, Theodore L; Yudin, Ashley I; Cherr, Gary N et al. (2003) Real-time observations of individual macaque sperm undergoing tight binding and the acrosome reaction on the zona pellucida. Biol Reprod 68:664-72
Tollner, T L; Overstreet, J W; Branciforte, D et al. (2002) Immunization of female cynomolgus macaques with a synthetic epitope of sperm-specific lactate dehydrogenase results in high antibody titers but does not reduce fertility. Mol Reprod Dev 62:257-64
Deng, X; Meyers, S A; Tollner, T L et al. (2002) Immunological response of female macaques to the PH-20 sperm protein following injection of recombinant proteins or synthesized peptides. J Reprod Immunol 54:93-115
Li, Ming-Wen; Yudin, Ashley I; Robertson, Kathryn R et al. (2002) Importance of glycosylation and disulfide bonds in hyaluronidase activity of macaque sperm surface PH-20. J Androl 23:211-9
Primakoff, Paul; Myles, Diana G (2002) Penetration, adhesion, and fusion in mammalian sperm-egg interaction. Science 296:2183-5

Showing the most recent 10 out of 61 publications