Immunization with a pentameric L1 fusion protein protects against papillomavirus infection

J Virol. 2001 Sep;75(17):7848-53. doi: 10.1128/jvi.75.17.7848-7853.2001.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • Capsid / chemistry
  • Capsid / genetics
  • Capsid / immunology*
  • Capsid / metabolism
  • Disease Models, Animal
  • Dogs
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Glutathione Transferase / chemistry
  • Glutathione Transferase / genetics
  • Glutathione Transferase / immunology
  • Glutathione Transferase / metabolism
  • Humans
  • Mouth / virology
  • Papillomaviridae / immunology*
  • Papillomavirus Infections / prevention & control*
  • Protein Conformation
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • Tumor Virus Infections / prevention & control*
  • Vaccination
  • Vaccines, Synthetic / immunology*
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Viral
  • Recombinant Fusion Proteins
  • Vaccines, Synthetic
  • Viral Vaccines
  • Glutathione Transferase