title: Immunization with a pentameric L1 fusion protein protects against papillomavirus infection.
abstract: The prophylactic papillomavirus vaccines currently in clinical trials are composed of viral L1 capsid protein that is synthesized in eukaryotic expression systems and purified in the form of virus-like particles (VLPs). To evaluate whether VLPs are necessary for effective vaccination, we expressed the L1 protein as a glutathione S-transferase (GST) fusion protein in Escherichia coli and assayed its immunogenic activity in an established canine oral papillomavirus (COPV) model that previously validated the efficacy of VLP vaccines. The GST-COPV L1 fusion protein formed pentamers, but these capsomere-like structures did not assemble into VLPs. Despite the lack of VLP formation, the GST-COPV L1 protein retained its native conformation as determined by reactivity with conformation-specific anti-COPV antibodies. Most importantly, the GST-COPV L1 pentamers completely protected dogs from high-dose viral infection of their oral mucosa. L1 fusion proteins expressed in bacteria represent an economical alternative to VLPs as a human papillomavirus vaccine.
authors.affiliation: Department of Pathology, Georgetown University School of Medicine, Washington, DC 20007, USA.
authors.forename: H
authors.initials: H
authors.lastname: Yuan
authors.forename: P A
authors.initials: PA
authors.lastname: Estes
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Newsome
authors.forename: V A
authors.initials: VA
authors.lastname: Olcese
authors.forename: R L
authors.initials: RL
authors.lastname: Garcea
authors.forename: R
authors.initials: R
authors.lastname: Schlegel
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002213:Capsid / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D009055:Mouth / Q000821:virology; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000517:prevention & control*; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D014412:Tumor Virus Infections / Q000517:prevention & control*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D005982:Glutathione Transferase