Targeting synthetic Human Papillomavirus (HPV) L2 disulfide-induced N-terminus conformational epitopes for pan-HPV vaccine development

Exp Mol Pathol. 2015 Oct;99(2):330-4. doi: 10.1016/j.yexmp.2015.06.021. Epub 2015 Jun 30.

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.

Conclusion: A cyclized L2 peptide has potential to be an excellent candidate to formulate a low-cost, broadly protective pan-oncogenic HPV vaccine.

Keywords: Cyclized synthetic peptide; Human Papillomavirus (HPV); L2 protein; Neutralizing antibody.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Capsid Proteins / immunology*
  • Disulfides / chemistry*
  • Disulfides / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / chemistry*
  • Epitopes / immunology*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Oncogene Proteins, Viral / immunology*
  • Papillomaviridae / immunology
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines / immunology
  • Papillomavirus Vaccines / therapeutic use
  • Peptide Fragments / immunology
  • Peptide Fragments / pharmacology*
  • Rabbits
  • Sequence Homology, Amino Acid
  • Vaccines, Synthetic / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Capsid Proteins
  • Disulfides
  • Epitopes
  • L2 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus Vaccines
  • Peptide Fragments
  • Vaccines, Synthetic