title: Analysis of a human sperm CD52 glycoform in primates: identification of an animal model for immunocontraceptive vaccine development.
abstract: Sperm agglutination antigen-1 (SAGA-1) is a human male reproductive tract glycoform of CD52. Unique modification of CD52 N-linked oligosaccharide chains in the epididymis and vas deferens results in the appearance of a carbohydrate epitope that is localized over the entire surface of human spermatozoa. SAGA-1 was characterized by the sperm-inhibitory murine monoclonal antibody (mAb) S19, and it is the target antigen of a human mAb (H6-3C4) associated with antibody-mediated infertility. Collectively, sperm surface localization, antibody inhibition of sperm function, and potential reproductive-tissue specificity identify SAGA-1 as an attractive candidate contraceptive immunogen. To establish an animal model for the study of SAGA-1 in immunologic infertility and immunocontraceptive development, we investigated the appearance of the S19 carbohydrate epitope in nonhuman primates. The S19 mAb demonstrated little to no immunoreactivity by Western blot analysis with protein extracts of spermatozoa from the baboon, marmoset, bonnet, cynomolgus, and pigtailed macaques. Immunohistochemical analysis identified CD52 in the bonnet monkey epididymis; however, the N-linked carbohydrate moiety recognized by the S19 mAb, and unique to SAGA-1, was absent. In contrast, the S19 carbohydrate epitope was identified in chimpanzee sperm extracts by Western blot analysis and in chimpanzee epididymal tissue sections by immunohistochemical analysis, indicating that it is conserved in this close relative of the human. Chimpanzee testis, seminal vesicle, and prostate do not express the S19 epitope. Although anti-CD52 immunoreactivity was identified in the spleen, the carbohydrate moiety recognized by the S19 mAb was absent, corroborating data in the human that demonstrated tissue-specific glycosylation of sperm CD52. Immunofluorescent analysis indicated that the chimpanzee homologue of sperm CD52 was present over the entire spermatozoon. In addition, the S19 mAb agglutinated chimpanzee spermatozoa in a manner similar to the effect observed on human spermatozoa. These data indicate that the distinctive carbohydrate moiety of human sperm CD52 is present in the chimpanzee, and they identify the chimpanzee as the most appropriate primate model to study the potential of this unique CD52 glycoform as a contraceptive immunogen.
authors.affiliation: Department of Cell Biology, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
authors.forename: Tod C
authors.initials: TC
authors.lastname: McCauley
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Kurth
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Norton
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Klotz
authors.forename: V Anne
authors.initials: VA
authors.lastname: Westbrook
authors.forename: A Jaganandha
authors.initials: AJ
authors.lastname: Rao
authors.forename: John C
authors.initials: JC
authors.lastname: Herr
authors.forename: Alan B
authors.initials: AB
authors.lastname: Diekman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis*; D000951:Antigens, Neoplasm / Q000032:analysis*; D000954:Antigens, Surface / Q000032:analysis* / Q000276:immunology*; D005075:Biological Evolution; D015153:Blotting, Western; D000074301:CD52 Antigen; D002144:Callithrix / Q000276:immunology; D003269:Contraception, Immunologic; D004822:Epididymis / Q000276:immunology; D000939:Epitopes / Q000032:analysis / Q000737:chemistry / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000032:analysis* / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D007163:Immunosorbent Techniques; D008252:Macaca fascicularis / Q000276:immunology; D008254:Macaca nemestrina / Q000276:immunology; D008255:Macaca radiata / Q000276:immunology; D008297:Male; D023421:Models, Animal; D002679:Pan troglodytes / Q000276:immunology; D010215:Papio / Q000276:immunology; D013045:Species Specificity; D013094:Spermatozoa / Q000276:immunology* / Q000502:physiology; D022642:Vaccines, Contraceptive
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D000939:Epitopes; D006023:Glycoproteins; C120760:SAGA-1 protein, human; D022642:Vaccines, Contraceptive