Efficacy of RG1-VLP vaccination against infections with genital and cutaneous human papillomaviruses

Christina Schellenbacher, Kihyuck Kwak, Dieter Fink, Saeed Shafti-Keramat, Bettina Huber, Christoph Jindra, Helena Faust, Joakim Dillner, Richard B.S. Roden, Reinhard Kirnbauer

Research output: Contribution to journalArticle

Abstract

Licensed human papillomavirus (HPV) vaccines, based on virus-like particles (VLPs) self-assembled from major capsid protein L1, afford type-restricted protection against HPV types 16/18/6/11 (or 16/18 for the bivalent vaccine), which cause 70% of cervical cancers (CxCas) and 90% of genital warts. However, they do not protect against less prevalent high-risk (HR) types causing 30% of CxCa, or cutaneous HPV. In contrast, vaccination with the minor capsid protein L2 induces low-level immunity to type-common epitopes. Chimeric RG1-VLP presenting HPV16 L2 amino acids 17-36 (RG1 epitope) within the DE-surface loop of HPV16 L1 induced cross-neutralizing antisera. We hypothesized that RG1-VLP vaccination protects against a large spectrum of mucosal and cutaneous HPV infections in vivo. Immunization with RG1-VLP adjuvanted with human-applicable alum-MPL (aluminum hydroxide plus 3-O-desacyl-4′-monophosphoryl lipid A) induced robust L2 antibodies (ELISA titers 2,500-12,500), which (cross-)neutralized mucosal HR HPV16/18/45/37/33/52/58/35/39/51/59/68/73/26/69/ 34/70, low-risk HPV6/11/32/40, and cutaneous HPV2/27/3/76 (titers 25-1,000) using native virion- or pseudovirion (PsV)-based assays, and a vigorous cytotoxic T lymphocyte response by enzyme-linked immunospot. In vivo, mice were efficiently protected against experimental vaginal challenge with mucosal HR PsV types HPV16/18/45/31/33/52/58/35/39/51/59/68/56/73/26/53/66/34 and low-risk HPV6/43/44. Enduring protection was demonstrated 1 year after vaccination. RG1-VLP is a promising next-generation vaccine with broad efficacy against all relevant mucosal and also cutaneous HPV types.

Original languageEnglish (US)
Pages (from-to)2706-2713
Number of pages8
JournalJournal of Investigative Dermatology
Volume133
Issue number12
DOIs
StatePublished - Dec 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Schellenbacher, C., Kwak, K., Fink, D., Shafti-Keramat, S., Huber, B., Jindra, C., Faust, H., Dillner, J., Roden, R. B. S., & Kirnbauer, R. (2013). Efficacy of RG1-VLP vaccination against infections with genital and cutaneous human papillomaviruses. Journal of Investigative Dermatology, 133(12), 2706-2713. https://doi.org/10.1038/jid.2013.253