Archives of Virology

, Volume 158, Issue 10, pp 2079–2088 | Cite as

Development of human papillomavirus chimaeric L1/L2 candidate vaccines

  • Marieta McGrath
  • Gillian K. de Villiers
  • Enid Shephard
  • Inga I. Hitzeroth
  • Edward P. Rybicki
Original Article

Abstract

Recombinant human papillomavirus (HPV) virus-like particle (VLP) vaccines based on the L1 capsid protein have been shown to be efficient prophylactic vaccines, albeit type-specific. As a first step to investigate the feasibility of extending protection against non-vaccine types, HPV-16 L1 chimaeras were generated. The region downstream of L1 amino acid (aa) 413 was replaced with selected cross-neutralising epitopes (aa 108-120; 56-81 and 17-36) derived from the HPV-16 L2 protein, generating proteins designated SAF, L2.56 and L2.17, respectively. The chimaera L1BPV containing BPV-1 L2 peptide aa 1-88 was similarly constructed. The chimaeras were evaluated for expression in insect cells; their ability to form particles was studied by electron microscopy, and their immunogenicity was evaluated in mice. SAF, L2.56 and L2.17 proteins were expressed to high concentrations in insect cells and elicited HPV-16 pseudovirus-neutralising anti-L1 antibodies. L2.56 and L2.17 also elicited anti-L2 antibodies. L1BPV was a poor vaccine candidate due to low levels of expression with concomitant lack of immunogenicity. All chimaeras assembled into tertiary structures. The results indicate that chimaeric L1 vaccines incorporating cross-neutralising L2 peptides could be promising second-generation prophylactic HPV vaccine candidates.

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Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • Marieta McGrath
    • 1
  • Gillian K. de Villiers
    • 1
  • Enid Shephard
    • 2
    • 3
    • 4
  • Inga I. Hitzeroth
    • 1
  • Edward P. Rybicki
    • 2
    • 1
  1. 1.Department of Molecular and Cell BiologyUniversity of Cape TownCape TownSouth Africa
  2. 2.Institute of Infectious Diseases and Molecular MedicineCape TownSouth Africa
  3. 3.Department of Medicine Faculty of Health SciencesUniversity of Cape TownObservatorySouth Africa
  4. 4.Medical Research CouncilTygerbergSouth Africa

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