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

9 Citations (Scopus)

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

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Cross Protection
Papillomavirus Vaccines
virus-like particles
Papillomaviridae
Virion
Human papillomavirus 16
vaccines
Human papillomavirus 18
chimerism
rabbits
Capsid Proteins
Rabbits
coat proteins
Human papillomavirus 2
epitopes
Epitopes
Gammapapillomavirus
Human papillomavirus 6
Virus-Like Particle Vaccines
Vaccines

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Boxus, M., Fochesato, M., Miseur, A., Mertens, E., Dendouga, N., Brendle, S., ... 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
Boxus, Mathieu ; Fochesato, Michel ; Miseur, Agnès ; Mertens, Emmanuel ; Dendouga, Najoua ; Brendle, Sarah ; Balogh, Karla K. ; Christensen, Neil D. ; Giannini, Sandra L. / Broad cross-protection is induced in preclinical models by a human papillomavirus vaccine composed of L1/L2 chimeric virus-like particles. In: Journal of virology. 2016 ; Vol. 90, No. 14. pp. 6314-6325.
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Boxus, M, Fochesato, M, Miseur, A, Mertens, E, Dendouga, N, Brendle, S, Balogh, KK, Christensen, ND & Giannini, SL 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, vol. 90, no. 14, pp. 6314-6325. https://doi.org/10.1128/JVI.00449-16

Broad cross-protection is induced in preclinical models by a human papillomavirus vaccine composed of L1/L2 chimeric virus-like particles. / Boxus, Mathieu; Fochesato, Michel; Miseur, Agnès; Mertens, Emmanuel; Dendouga, Najoua; Brendle, Sarah; Balogh, Karla K.; Christensen, Neil D.; Giannini, Sandra L.

In: Journal of virology, Vol. 90, No. 14, 01.01.2016, p. 6314-6325.

Research output: Contribution to journalArticle

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AU - Boxus, Mathieu

AU - Fochesato, Michel

AU - Miseur, Agnès

AU - Mertens, Emmanuel

AU - Dendouga, Najoua

AU - Brendle, Sarah

AU - Balogh, Karla K.

AU - Christensen, Neil D.

AU - Giannini, Sandra L.

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