title: Studies towards the potential of poliovirus as a vector for the expression of HPV 16 virus-like-particles.
abstract: Development of human cervical carcinomas is associated with infection by certain human papillomavirus (HPV) types. Thus, protection against HPV infection through vaccination may prevent development of cervical cancer. The purpose of this study was to investigate the possibility of using a poliovirus recombinant vector to induce immunity against HPV. A poliovirus recombinant was constructed which contained the complete coding sequence of the HPV 16 major capsid protein L1, between the P1 and P2 region of the poliovirus polyprotein. A replication-competent virus was obtained after transfection of the recombinant RNA into tissue culture cells. Electron microscopically examination of cells infected with the poliovirus-HPV L1 recombinant indicated that HPV 16 L1 self-assembles into virus-like particles. To investigate the immunological response in vivo, susceptible transgenic mice carrying the poliovirus receptor were infected with the recombinant poliovirus. In all mice a modest but consistent immune response against HPV 16 was observed. Based on these results, the potential for picornavirus-derived vectors in vaccine development against HPV infection is discussed.
authors.affiliation: University Medical Center Nijmegen, Nijmegen Center for Molecular Life Sciences, Department of Medical Microbiology, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Frank J M
authors.initials: FJ
authors.lastname: van Kuppeveld
authors.forename: Arjan
authors.initials: A
authors.lastname: de Jong
authors.forename: Henri B P M
authors.initials: HB
authors.lastname: Dijkman
authors.forename: Raul
authors.initials: R
authors.lastname: Andino
authors.forename: Willem J G
authors.initials: WJ
authors.lastname: Melchers
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D036022:Capsid Proteins; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008854:Microscopy, Electron / Q000379:methods; D008957:Models, Genetic; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics* / Q000254:growth & development / Q000648:ultrastructure; D017955:Poliovirus / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014709:Vero Cells; D014771:Virion / Q000235:genetics*
chemical_list: D000914:Antibodies, Viral; D036022:Capsid Proteins; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral; D011994:Recombinant Proteins