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 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

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Viruses
Virion
Vaccination
Skin
Infection
Capsid Proteins
Epitopes
Vaccines
Immunization
Aluminum Hydroxide
Papillomavirus Vaccines
T-cells
Human papillomavirus 18
Condylomata Acuminata
Papillomavirus Infections
Human papillomavirus 16
Cytotoxic T-Lymphocytes
Immune Sera
Assays
Uterine Cervical Neoplasms

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Schellenbacher, C., Kwak, K., Fink, D., Shafti-Keramat, S., Huber, B., Jindra, C., ... 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

Efficacy of RG1-VLP vaccination against infections with genital and cutaneous human papillomaviruses. / Schellenbacher, Christina; Kwak, Kihyuck; Fink, Dieter; Shafti-Keramat, Saeed; Huber, Bettina; Jindra, Christoph; Faust, Helena; Dillner, Joakim; Roden, Richard S; Kirnbauer, Reinhard.

In: Journal of Investigative Dermatology, Vol. 133, No. 12, 12.2013, p. 2706-2713.

Research output: Contribution to journalArticle

Schellenbacher, C, Kwak, K, Fink, D, Shafti-Keramat, S, Huber, B, Jindra, C, Faust, H, Dillner, J, Roden, RS & Kirnbauer, R 2013, 'Efficacy of RG1-VLP vaccination against infections with genital and cutaneous human papillomaviruses', Journal of Investigative Dermatology, vol. 133, no. 12, pp. 2706-2713. https://doi.org/10.1038/jid.2013.253
Schellenbacher, Christina ; Kwak, Kihyuck ; Fink, Dieter ; Shafti-Keramat, Saeed ; Huber, Bettina ; Jindra, Christoph ; Faust, Helena ; Dillner, Joakim ; Roden, Richard S ; Kirnbauer, Reinhard. / Efficacy of RG1-VLP vaccination against infections with genital and cutaneous human papillomaviruses. In: Journal of Investigative Dermatology. 2013 ; Vol. 133, No. 12. pp. 2706-2713.
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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.",
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