Chimeric Human papillomavirus type 16 (HPV-16) L1 particles presenting the common neutralizing epitope for the L2 minor capsid protein of HPV-6 and HPV-16

Arvind Varsani, Anna Lise Williamson, Debbie De Villiers, Inga Becker, Neil D. Christensen, Edward P. Rybicki

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Both the Human papillomavirus (HPV) major (L1) and minor (L2) capsid proteins have been well investigated as potential vaccine candidates. The L1 protein first oligomerizes into pentamers, and these capsomers assemble into virus-like particles (VLPs) that are highly immunogenic. Here we examine the potential of using HPV type 16 (HPV-16) L1 subunits to display a well-characterized HPV-16 L2 epitope (LVEETSFIDAGAP), which is a common-neutralizing epitope for HPV types 6 and 16, in various regions of the L1 structure. The L2 sequence was introduced by PCR (by replacing 13 codons) into sequences coding for L1 surface loops D-E (ChiΔC-L2), E-F (ChiΔA-L2), and an internal loop C-D (ChiΔH-L2); into the h4 helix (ChiΔF-L2); and between h4 and β-J structural regions (ChiΔE-L2). The chimeric protein product was characterized using a panel of monoclonal antibodies (MAbs) that bind to conformational and linear epitopes, as well as a polyclonal antiserum raised to the L2 epitope. All five chimeras reacted with the L2 serum. ChiΔA-L2, ChiΔE-L2, and ChiΔF-L2 reacted with all the L1 antibodies, ChiΔC-L2 did not bind H16:V5 and H16:E70, and ChiΔH-L2 did not bind any conformation-dependent MAb. The chimeric particles elicited high-titer anti-L1 immune responses in BALB/c mice. Of the five chimeras tested only ChiΔH-L2 did not elicit an L2 response, while ChiΔF-L2 elicited the highest L2 response. This study provides support for the use of PV particles as vectors to deliver various epitopes in a number of locations internal to the L1 protein and for the potential of using chimeric PV particles as multivalent vaccines. Moreover, it contributes to knowledge of the structure of HPV-16 L1 VLPs and their derivatives.

Original languageEnglish (US)
Pages (from-to)8386-8393
Number of pages8
JournalJournal of virology
Volume77
Issue number15
DOIs
StatePublished - Aug 2003

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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