Broad cross-protection is induced in preclinical models by a human papillomavirus vaccine composed of L1/L2 chimeric virus-like particles

Mathieu Boxus, Michel Fochesato, Agnès Miseur, Emmanuel Mertens, Najoua Dendouga, Sarah Brendle, Karla K. Balogh, Neil D. Christensen, Sandra L. Giannini

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

At least 15 high-risk human papillomaviruses (HPVs) are linked to anogenital preneoplastic lesions and cancer. Currently, thereare three licensed prophylactic HPV vaccines based on virus-like particles (VLPs) of the L1 major capsid protein from HPV-2, -4,or -9, including the AS04-adjuvanted HPV-16/18 L1 vaccine. The L2 minor capsid protein contains HPV-neutralizing epitopesthat are well conserved across numerous high-risk HPVs. Therefore, the objective of our study was to assess the capacity tobroaden vaccine-mediated protection using AS04-adjuvanted vaccines based on VLP chimeras of L1 with one or two L2 epitopes.Several chimeric VLPs were constructed by inserting L2 epitopes within the DE loop and/or C terminus of L1. Based on theshape, yield, size, and immunogenicity, one of seven chimeras was selected for further evaluation in mouse and rabbit challengemodels. The chimeric VLP consisted of HPV-18 L1 with insertions of HPV-33 L2 (amino acid residues 17 to 36; L1 DE loop) andHPV-58 L2 (amino acid residues 56 to 75; L1 C terminus). This chimeric L1/L2 VLP vaccine induced persistent immune responsesand protected against all of the different HPVs evaluated (HPV-6, -11, -16, -31, -35, -39, -45, -58, and -59 as pseudovirionsor quasivirions) in both mouse and rabbit challenge models. The degree and breadth of protection in the rabbit were furtherenhanced when the chimeric L1/L2 VLP was formulated with the L1 VLPs from the HPV-16/18 L1 vaccine. Therefore, the novelHPV-18 L1/L2 chimeric VLP (alone or in combination with HPV-16 and HPV-18 L1 VLPs) formulated with AS04 has the potentialto provide broad protective efficacy in human subjects.

Original languageEnglish (US)
Pages (from-to)6314-6325
Number of pages12
JournalJournal of virology
Volume90
Issue number14
DOIs
StatePublished - Jan 1 2016

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Boxus, M., Fochesato, M., Miseur, A., Mertens, E., Dendouga, N., Brendle, S., Balogh, K. K., Christensen, N. D., & Giannini, S. L. (2016). Broad cross-protection is induced in preclinical models by a human papillomavirus vaccine composed of L1/L2 chimeric virus-like particles. Journal of virology, 90(14), 6314-6325. https://doi.org/10.1128/JVI.00449-16