Abstract

In this proposal we plan to follow two different strategies for immunocontraception in males. Both of these strategies are aimed at developing an effective immunocontraceptive in the absence of undesirable immune responses such as immune orchitis or other inflammation in the male reproductive tract. Both active and passive immunizations are proposed. (1) For active immunizations we will use a peptide that contains a single antibody-binding site (epitope) that is only present on the surface of post-testicular sperm. This epitope is created by proteolytic processing of the sperm-specific surface protein, PH-30, during epididymal maturation. The epitope is absent from other regions of the male reproductive tract including the testis and epididymal epithelium. A monoclonal antibody (MAb) to the epitope blocks fertilization. (2) The second approach, designed to avoid adverse cell-mediated immune responses, will be passive immunization with syngeneic MAbs to the PH-29 or PH-30 proteins.

  Funding Agency

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 #
3U54HD029125-06S1
Application #
3712495
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1996
Total Cost
Indirect Cost

  Institution

Name
University of California Davis
Department
Type
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618

  Publications

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

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