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O01.5 Efficacy of RG1-VLP Vaccination Against Genital and Cutaneous Human Papillomaviruses in Vitro and in Vivo
  1. C Schellenbacher1,
  2. K Kwak2,
  3. D Fink3,
  4. S Shafti-Keramat1,
  5. B Huber1,
  6. C Jindra1,
  7. R Roden2,
  8. R Kirnbauer1
  1. 1Medical University Vienna, Division of Immunology, Allergy and Infectious Diseases (DIAID), Vienna, Austria
  2. 2Johns Hopkins University, Baltimore, MD, United States
  3. 3Institute of Laboratory Animal Science, Veterinary University Vienna, Austria, Vienna, Austria

Abstract

Licensed human papillomavirus (HPV) vaccines, based on virus-like particles (VLP) self-assembled from major capsid protein L1, afford type-restricted protection against types 16/18/6/11 (or 16/18 for the bivalent vaccine), which cause 70% of cervical carcinomas (Cxca) and 90% of genital warts. However, they do not protect against less prevalent high-risk types causing 30% of CxCa, or cutaneous HPV. The minor capsid protein L2 confers low-level immunity to type-common epitopes.

Chimeric RG1-VLP presenting HPV16L2 amino acids 17–36 (RG1 epitope) within the DE-surface loop of HPV16L1 induce cross-neutralisation in vitro. We hypothesised, that RG1-VLP vaccination protects against a large spectrum of mucosal and cutaneous HPV infections in vivo.

L2-specific antibody and CTL responses in RG1-VLP vaccinated rabbits were determined by ELISA and ELISPOT assays. Cross-neutralisation was analysed using native or pseudovirion (PsV) assays. Vaccine efficacy in vivo was determined in a mouse genital challenge model.

Immunization with RG1-VLP adjuvanted with human-applicable alum-MPL induced robust L2 antibodies (ELISA titers 2,500–12,500), which cross-neutralised mucosal high-risk HPV26/33/35/39/68/59/68/73/69/53/34, low-risk HPV6/11/32/40/44/70, and cutaneous HPV2/27/3/76 (titers 25–1,000), and a vigorous CTL response. In vivo, mice were efficiently protected against experimental vaginal challenge with mucosal high-risk 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.

  • HPV
  • Vaccine

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