Phase II studies to select the formulation of a multivalent HPV L1 virus-like particle (VLP) vaccine

Alain Luxembourg, Darron Brown, Celine Bouchard, Anna R. Giuliano, Ole Erik Iversen, Elmar A. Joura, Mary E. Penny, Jaime A. Restrepo, Josefina Romaguera, Roger Maansson, Erin Moeller, Michael Ritter, Joshua Chen

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Our objective was to develop a multivalent prophylactic HPV vaccine that protects against infection and disease caused by HPV16/18 (oncogenic types in existing prophylactic vaccines) plus additional oncogenic types by conducting 3 Phase II studies comparing the immunogenicity (i.e., anti-HPV6/11/16/18 geometric mean titers [GMT]) and safety of 7 vaccine candidates with the licensed quadrivalent HPV6/11/16/18 vaccine (qHPV vaccine) in young women ages 16–26. In the first study (Study 1), subjects received one of 3 dose formulations of an 8-valent HPV6/11/16/18/31/45/52/58 vaccine or qHPV vaccine (control). In Study 2, subjects received one of 3 dose formulations (termed low-, mid-, and high-dose formulations, respectively) of a 9-valent HPV6/11/16/18/31/33/45/52/58 vaccine (9vHPV vaccine) or qHPV vaccine (control). In Study 3, subjects concomitantly received qHPV vaccine plus 5-valent HPV31/33/45/52/58 or qHPV vaccine plus placebo (control). All vaccines were administered at day 1/month 2/month 6. In studies 1 and 3, anti-HPV6/ 11/16/18 GMTs at month 7 were non-inferior in the experimental arms compared with the control arm; however, there was a trend for lower antibody responses for all 4 HPV types. In Study 2, this immune interference was overcome with the mid- and high-dose formulations of the 9vHPV vaccine by increasing antigen and adjuvant doses. In all 3 studies, all vaccine candidates were strongly immunogenic with respect to HPV31/33/45/52/58 and were well tolerated. Based on the totality of the results, the middle dose formulation of the 9vHPV vaccine was selected for Phase III evaluation. Each 0.5mL dose contains 30μg/40μg/60μg/40μg/20μg/20μg/20μg/20μg/20μg of HPV6/11/16/18/31/33/45/52/58 viruslike particles, and 500μg of amorphous aluminum hydroxyphosphate sulfate adjuvant.ClinicalTrials.gov numbers NCT00260039, NCT00543543, and NCT00551187.

Original languageEnglish (US)
Pages (from-to)1313-1322
Number of pages10
JournalHuman Vaccines and Immunotherapeutics
Volume11
Issue number6
DOIs
StatePublished - Jan 1 2015

Keywords

  • Dose selection
  • Formulation
  • HPV
  • Immunogenicity
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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    Luxembourg, A., Brown, D., Bouchard, C., Giuliano, A. R., Iversen, O. E., Joura, E. A., Penny, M. E., Restrepo, J. A., Romaguera, J., Maansson, R., Moeller, E., Ritter, M., & Chen, J. (2015). Phase II studies to select the formulation of a multivalent HPV L1 virus-like particle (VLP) vaccine. Human Vaccines and Immunotherapeutics, 11(6), 1313-1322. https://doi.org/10.1080/21645515.2015.1012010