title: Viral vectored immunocontraception: screening of multiple fertility antigens using murine cytomegalovirus as a vaccine vector.
abstract: Mouse cytomegalovirus (MCMV) has previously been used as a vaccine vector for viral vectored immunocontraception (VVIC). MCMV expressing murine zona pellucida 3 (mZP3) induces long term infertility in up to 100% of female BALB/c mice following a single inoculation. Whilst a large number of antigens have been investigated as potential immunocontraceptive vaccines, it has been difficult to compare these antigens as few studies have used identical approaches or even animal species. Here a range of protein and polyepitope antigens, all expressed by MCMV, were tested for the ability to sterilise female mice. The antigens tested were bone morphogenic protein 15 (BMP15), oviduct glycoprotein (OGP) and ubiquitin-tagged mZP3. In addition, four polyepitope constructs that contain rodent or mouse specific epitopes were tested. This study found that when expressed by an MCMV vector, only full-length mZP3 or ubiquitin-tagged mZP3 induced infertility in female mice. BMP15 and OGP had no effect. Of the four polyepitopes tested, one had a partial effect on fertility. These data indicate that while MCMV is an effective vector for VVIC, the antigen used needs to be tested empirically. The partial infertility seen in mice infected with one of the polyepitope vaccines is a promising finding suggesting that it may be possible to combine a species specific virus with a species specific antigen for use as a disseminating mouse control agent.
authors.affiliation: Microbiology and Immunology, School of Biomedical, Biomolecular and Chemical Sciences, M502, The University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, Australia. aredwood@cyllene.uwa.edu.au
authors.forename: Alec J
authors.initials: AJ
authors.lastname: Redwood
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Harvey
authors.forename: Megan
authors.initials: M
authors.lastname: Lloyd
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Lawson
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hardy
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Shellam
mesh_terms: D000818:Animals; D055430:Bone Morphogenetic Protein 15; D003269:Contraception, Immunologic / Q000379:methods*; D003587:Cytomegalovirus / Q000378:metabolism*; D004527:Egg Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D000072216:Zona Pellucida Glycoproteins
chemical_list: C525902:Bmp15 protein, mouse; D055430:Bone Morphogenetic Protein 15; D004527:Egg Proteins; C525898:Gdf9 protein, mouse; D006023:Glycoproteins; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000072216:Zona Pellucida Glycoproteins