title: VLPs displaying a single L2 epitope induce broadly cross-neutralizing antibodies against human papillomavirus.
abstract: BACKGROUND
  Virus-like Particles (VLPs) display can be used to increase the immunogenicity of heterologous antigens. Here, we report the use of a bacteriophage MS2-based VLP display platform to develop a monovalent vaccine targeting a broadly neutralizing epitope in the minor capsid protein human papillomavirus (HPV) that provides broad protection from diverse HPV types in a mouse pseudovirus infection model.
  
  
  RESULTS
  Peptides spanning a previously described cross-neutralizing epitope from HPV type 16 were genetically inserted at the N-terminus of MS2 bacteriophage coat protein. Three of the four recombinant L2-coat proteins assembled into VLPs. L2-VLPs elicited high-titer anti-L2 antibodies in mice, similar to recombinant VLPs that we had previously made in which the L2 peptide was displayed on a surface-exposed loop on VLPs of a related bacteriophage, PP7. Somewhat surprisingly, L2-MS2 VLPs elicited antibodies that were much more broadly cross-reactive with L2 peptides from diverse HPV isolates than L2-PP7 VLPs. Similarly, mice immunized with L2-MS2 VLPs were protected from genital and cutaneous infection by highly diverse HPV pseudovirus types.
  
  
  CONCLUSIONS
  We show that peptides can be displayed in a highly immunogenic fashion at the N-terminus of MS2 coat protein VLPs. A VLP-based vaccine targeting HPV L2 elicits broadly cross-reactive and cross-protective antibodies to heterologous HPV types. L2-VLPs could serve as the basis of a broadly protective second generation HPV vaccine.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America. etumban@salud.unm.edu
authors.forename: Ebenezer
authors.initials: E
authors.lastname: Tumban
authors.forename: Julianne
authors.initials: J
authors.lastname: Peabody
authors.forename: Mitchell
authors.initials: M
authors.lastname: Tyler
authors.forename: David S
authors.initials: DS
authors.lastname: Peabody
authors.forename: Bryce
authors.initials: B
authors.lastname: Chackerian
mesh_terms: D000818:Animals; D036022:Capsid Proteins; D004195:Disease Models, Animal; D000939:Epitopes; D005260:Female; D017909:Levivirus / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008957:Models, Genetic; D009500:Neutralization Tests; D009856:Oncogene Proteins, Viral; D027383:Papillomaviridae / Q000737:chemistry*; D030361:Papillomavirus Infections / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000276:immunology; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D058425:Vaccines, Virus-Like Particle / Q000737:chemistry*; D014780:Viruses / Q000737:chemistry*
chemical_list: D036022:Capsid Proteins; D000939:Epitopes; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D010455:Peptides; D058425:Vaccines, Virus-Like Particle