The mission of this Center is to develop and test a safe, effective, reversible contraceptive vaccine. Emphasis will be placed upon a vaccine for females, consisting of one or more recombinant gamete associated immunogens which elicit immunological responses that function to prevent fertilization. The Center will coordinate research and development activities encompassing eight stages of a product development program: 1) Fundamental discovery and evaluation of gamete specific molecules (vaccinogens) and their antigenic determinants derived from the sperm, egg, egg investments, or accessory reproductive organs; 2) Engineering of genes encoding specific vaccinogens into appropriate expression systems or manufacture of synthetic peptides; 3) Production and purification of recombinant vaccinogens under good laboratory practices (GLP); 4) Formulation of vaccine doses; 5) Small animal and primate testing of vaccine formulations for immunogenicity, safety and efficacy; 6) Evaluation of mechanisms of vaccine action; 7) Human trials; and 8) Development of diagnostics to monitor infertility status in recipients of effective vaccines. Four Research Projects will be continued: The human sperm autoantigen SP17 will be tested for immunogenicity and fertility in mice and monkeys (O'Rand). The functional role of the sperm specific isoform of calpastatin will be evaluated by targeted gene disruption in mice, and contraceptive efficiency of calpastatin peptides will be evaluated in monkeys separately and in conjunction with LDHC-4 peptides (Goldberg). Studies of T and B cell epitopes on ZP3 will be extended to ZP2 to identify peptides that elicit infertility without oophoritis in mice and primates (Tung). Sperm surface proteins will be microsequenced, their cDNAs cloned, and the encoded proteins evaluated as vaccine immunogens using a detailed 2-D protein database of vectorially labeled human sperm surface proteins (Herr). Specialized Cores will support the Center's mission by providing shared laboratory resources and expertise critical to the development and testing of recombinant contraceptive vaccines. These facilities will evaluate tissue specificity of gamete vaccinogens at both protein and DNA levels (Core A); express vaccine genes and synthesize recombinant vaccinogens under good laboratory practices (Core B); evaluate are in vitro effects of antibodies to contraceptive immunogens on sperm function (Core C); maintain macaques for immunogenicity and efficacy testing of vaccine formulations (Core D); undertake and coordinate clinical studies (Core E); and administer and integrate activities of the overall Center (Core F). A multi-institutional interdisciplinary group of principal investigators with solid experience in the discovery and evaluation of candidate contraceptive vaccine immunogens has been assembled. Industrial associates will provide conceptual and financial support to the program in the areas of regulatory affairs, preclinical and clinical trials.

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 #
5U54HD029099-09
Application #
6164895
Study Section
Special Emphasis Panel (SRC (UT))
Program Officer
Blithe, Diana
Project Start
1991-09-30
Project End
2002-02-28
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
9
Fiscal Year
2000
Total Cost
$2,041,686
Indirect Cost
Name
University of Virginia
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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Shumilin, Igor A; Cymborowski, Marcin; Chertihin, Olga et al. (2012) Identification of unknown protein function using metabolite cocktail screening. Structure 20:1715-25
Naaby-Hansen, Soren; Herr, John C (2010) Heat shock proteins on the human sperm surface. J Reprod Immunol 84:32-40
Naaby-Hansen, Soren; Diekman, Alan; Shetty, Jagathpala et al. (2010) Identification of calcium-binding proteins associated with the human sperm plasma membrane. Reprod Biol Endocrinol 8:6
Klotz, Kenneth L; Coppola, Michael A; Labrecque, Michel et al. (2008) Clinical and consumer trial performance of a sensitive immunodiagnostic home test that qualitatively detects low concentrations of sperm following vasectomy. J Urol 180:2569-76
Kurth, Barbara E; Digilio, Laura; Snow, Phillip et al. (2008) Immunogenicity of a multi-component recombinant human acrosomal protein vaccine in female Macaca fascicularis. J Reprod Immunol 77:126-41
Herr, John C; Chertihin, Olga; Digilio, Laura et al. (2008) Distribution of RNA binding protein MOEP19 in the oocyte cortex and early embryo indicates pre-patterning related to blastomere polarity and trophectoderm specification. Dev Biol 314:300-16
Shetty, Jagathpala; Bronson, Richard A; Herr, John C (2008) Human sperm protein encyclopedia and alloantigen index: mining novel allo-antigens using sera from ASA-positive infertile patients and vasectomized men. J Reprod Immunol 77:23-31
Xu, Bingfang; Hao, Zhonglin; Jha, Kula N et al. (2008) TSKS concentrates in spermatid centrioles during flagellogenesis. Dev Biol 319:201-10
Xu, Bingfang; Hao, Zhonglin; Jha, Kula N et al. (2008) Targeted deletion of Tssk1 and 2 causes male infertility due to haploinsufficiency. Dev Biol 319:211-22

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