title: Targeting synthetic Human Papillomavirus (HPV) L2 disulfide-induced N-terminus conformational epitopes for pan-HPV vaccine development.
abstract: BACKGROUND
  Current vaccines against Human Papillomavirus (HPV) are highly effective and based on recombinant virus-like particles (VLPs) of the major capsid protein L1. Since these vaccines are HPV type-specific and expensive for global implementation, an alternative, broader-spectrum immunogen would be the N-terminus of the minor capsid protein L2 that induces low titered broadly cross-neutralizing antibodies. Here we analyzed the reactivity of different synthetic L2 peptides containing N-terminus amino acids 17-36 in order to test their antigenicity.
  
  
  METHODS
  Different synthetic peptides were designed to target the 17-36 amino acid sequences, present in highly antigenic amino-terminus of L2 protein. Six different peptides including Cys22-Cys28 disulfide bonded cyclized L2 peptide were examined for their antigenicity against mouse monoclonal antibody RG-1 and rabbit polyclonal antisera to HPV L2 by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Here we report that the cyclized form of synthetic L2 peptide, which is formed through Cys22-Cys28 disulfide bridges, has the highest reactivity to antibodies than other synthetic L2 peptides.
  
  
  CONCLUSIONS
  A cyclized L2 peptide has potential to be an excellent candidate to formulate a low-cost, broadly protective pan-oncogenic HPV vaccine.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA; James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA. Electronic address: sujita.khanal@louisville.edu.
authors.forename: Sujita
authors.initials: S
authors.lastname: Khanal
authors.affiliation: James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA; Emergency Medicine Associate, Vancouver, WA, USA. Electronic address: ericdferraris@gmail.com.
authors.forename: Eric Daniel
authors.initials: ED
authors.lastname: Ferraris
authors.affiliation: James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA. Electronic address: m0zahi01@louisville.edu.
authors.forename: Maryam
authors.initials: M
authors.lastname: Zahin
authors.affiliation: James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA; Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA. Electronic address: j0joh001@louisville.edu.
authors.forename: Joongho
authors.initials: J
authors.lastname: Joh
authors.affiliation: James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA; Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA. Electronic address: sjghim01@louisville.edu.
authors.forename: Shin-je
authors.initials: SJ
authors.lastname: Ghim
authors.affiliation: James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA. Electronic address: abjens01@louisville.edu.
authors.forename: Alfred Bennett
authors.initials: AB
authors.lastname: Jenson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D036022:Capsid Proteins / Q000276:immunology*; D004220:Disulfides / Q000737:chemistry* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000276:immunology / Q000627:therapeutic use; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D004220:Disulfides; D000939:Epitopes; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D010446:Peptide Fragments; D014614:Vaccines, Synthetic
keywords: Cyclized synthetic peptide; Human Papillomavirus (HPV); L2 protein; Neutralizing antibody