title: Immunogenicity of a multi-component recombinant human acrosomal protein vaccine in female Macaca fascicularis.
abstract: A vaccine formula comprised of five recombinant human intra-acrosomal sperm proteins was inoculated into female monkeys to test whether specific antibodies to each component immunogen could be elicited in sera and whether antibodies elicited by the vaccine affected in vitro fertilization. Acrosomal proteins, ESP, SLLP-1, SAMP 32, SP-10 and SAMP 14, were expressed with his-tags, purified by nickel affinity chromatography and adsorbed to aluminum hydroxide. Five female cynomolgus monkeys were inoculated intramuscularly three times at monthly intervals. All five monkeys developed both IgG and IgA serum responses to each recombinant immunogen on Western blots. Each serum stained the acrosome of human sperm and bound to the cognate native protein on Western blots of human sperm extracts. By ELISA, all monkeys developed IgG to each immunogen, with the highest average absorbance values to ESP, SAMP 32 and SP-10, followed by lower values for SLLP-1 and SAMP 14. IgA was also generated to each component immunogen with the highest average absorbance values to SLLP-1 and SP-10. For antigens that induced an IgA response, the duration of the IgA response was longer than the IgG response to the same antigens. This study supports the concept that a multivalent contraceptive vaccine may be administered to female primates evoking both peripheral (IgG) and mucosal (IgA) responses to each component immunogen following an intramuscular route of inoculation with a mild adjuvant, aluminum hydroxide, approved for human use.
authors.affiliation: The Center for Research in Contraception and Reproductive Health, Department of Cell Biology, University of Virginia, School of Medicine, P.O. Box 800732, Charlottesville, VA 22908-0732, USA.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Kurth
authors.forename: Laura
authors.initials: L
authors.lastname: Digilio
authors.forename: Phillip
authors.initials: P
authors.lastname: Snow
authors.forename: Leigh Ann
authors.initials: LA
authors.lastname: Bush
authors.forename: Michael
authors.initials: M
authors.lastname: Wolkowicz
authors.forename: Jagathpala
authors.initials: J
authors.lastname: Shetty
authors.forename: Arabinda
authors.initials: A
authors.lastname: Mandal
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Hao
authors.forename: P Prabhakara
authors.initials: PP
authors.lastname: Reddi
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Flickinger
authors.forename: John C
authors.initials: JC
authors.lastname: Herr
mesh_terms: D000177:Acrosome / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology*; D006224:Cricetinae; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D008252:Macaca fascicularis; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D018716:Molecular Mimicry; D011956:Receptors, Cell Surface / Q000276:immunology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology*; D029589:Seminal Plasma Proteins / Q000276:immunology; D013084:Sperm-Ovum Interactions / Q000276:immunology; D014611:Vaccination; D022642:Vaccines, Contraceptive / Q000276:immunology
chemical_list: C512729:ACRV1 protein, human; D000941:Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007519:Isoantigens; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C455113:SPACA1 protein, human; C490560:SPACA3 protein, human; C477160:SPACA4 protein, human; D029589:Seminal Plasma Proteins; D022642:Vaccines, Contraceptive