A male genital tract-specific carbohydrate epitope on human CD52: implications for immunocontraception.
The identification of unique sperm surface epitopes that are not expressed or exposed in the female reproductive tract is a key element in the development of antibody-based contraceptives. Western blotting and immunohistochemistry were performed to define the tissue distribution of the S19 epitope, which has been proposed as a target for immunocontraception. S19 is an IgG1 murine monoclonal antibody (mAb) directed to an N-linked carbohydrate epitope on a 15-25 kDa glycoprotein, sperm agglutination antigen-1 (SAGA-1), containing a peptide core identical to that of the lymphocytic surface protein CD52. In this study, the S19 epitope was shown to be absent from human lymphocytes, demonstrating a distinction between this epitope and the CAMPATH epitope that is recognized by an antibody against the terminal tripeptide and GPI-anchor of CD52. Further tissue specificity analysis identified the S19 epitope in the epithelium of the human epididymis and vas deferens, as well as on both epididymal and ejaculated spermatozoa. In contrast, the S19 epitope was absent in the five human female reproductive tract and 18 other somatic tissues tested. These results support the use of the S19 epitope as a contraceptive immunogen and the suitability of the S19 mAb as an intravaginal contraceptive. To test the agglutinating activity of the S19 mAb in a formulation designed for vaginal use, S19 mAb were bound to the surface of Novasomes, a multilamellar liposome delivery vehicle. S19-Novasome formulations agglutinated human spermatozoa and were as effective as unbound S19 mAb, demonstrating the feasibility of spermistatic contraceptives targeted to the male reproductive tract specific carbohydrate epitope.
Norton
E J
EJ
Department of Cell Biology, Center for Recombinant Gamete Contraceptive Vaccinogens, University of Virginia Health System, Charlottesville, VA 22908, USA.
Diekman
A B
AB
Westbrook
V A
VA
Mullins
D W
DW
Klotz
K L
KL
Gilmer
L L
LL
Thomas
T S
TS
Wright
D C
DC
Brisker
J
J
Engelhard
V H
VH
Flickinger
C J
CJ
Herr
J C
JC
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D015153:Blotting, Western; D000074301:CD52 Antigen; D002241:Carbohydrates / Q000276:immunology*; D003269:Contraception, Immunologic; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D005455:Fluorescent Antibody Technique; D005837:Genitalia, Male / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009928:Organ Specificity / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D002241:Carbohydrates; D000939:Epitopes; D006023:Glycoproteins