title: Randomized Open Trial Comparing 2-Dose Regimens of the Human Papillomavirus 16/18 AS04-Adjuvanted Vaccine in Girls Aged 9-14 Years Versus a 3-Dose Regimen in Women Aged 15-25 Years.
abstract: BACKGROUND
  This randomized, open trial compared regimens including 2 doses (2D) of human papillomavirus (HPV) 16/18 AS04-adjuvanted vaccine in girls aged 9-14 years with one including 3 doses (3D) in women aged 15-25 years.
  
  
  METHODS
  Girls aged 9-14 years were randomized to receive 2D at months 0 and 6 (M0,6; (n = 550) or months 0 and 12 (M0,12; n = 415), and women aged 15-25 years received 3D at months 0, 1, and 6 (n = 482). End points included noninferiority of HPV-16/18 antibodies by enzyme-linked immunosorbent assay for 2D (M0,6) versus 3D (primary), 2D (M0,12) versus 3D, and 2D (M0,6) versus 2D (M0,12); neutralizing antibodies; cell-mediated immunity; reactogenicity; and safety. Limits of noninferiority were predefined as <5% difference in seroconversion rate and <2-fold difference in geometric mean antibody titer ratio.
  
  
  RESULTS
  One month after the last dose, both 2D regimens in girls aged 9-14 years were noninferior to 3D in women aged 15-25 years and 2D (M0,12) was noninferior to 2D (M0,6). Geometric mean antibody titer ratios (3D/2D) for HPV-16 and HPV-18 were 1.09 (95% confidence interval, .97-1.22) and 0.85 (.76-.95) for 2D (M0,6) versus 3D and 0.89 (.79-1.01) and 0.75 (.67-.85) for 2D (M0,12) versus 3D. The safety profile was clinically acceptable in all groups.
  
  
  CONCLUSIONS
  The 2D regimens for the HPV-16/18 AS04-adjuvanted vaccine in girls aged 9-14 years (M0,6 or M0,12) elicited HPV-16/18 immune responses that were noninferior to 3D in women aged 15-25 years.
  
  
  BACKGROUND
  NCT01381575.
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Thanyawee
authors.initials: T
authors.lastname: Puthanakit
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Huang
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung University College of Medicine, Kweishan, Taoyuan.
authors.forename: Cheng-Hsun
authors.initials: CH
authors.lastname: Chiu
authors.affiliation: Department of Pediatrics, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: Ren-Bin
authors.initials: RB
authors.lastname: Tang
authors.affiliation: Central Laboratory and Vaccination Centre, Stiftung Juliusspital, Würzburg, Germany.
authors.forename: Tino F
authors.initials: TF
authors.lastname: Schwarz
authors.affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Cá Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Esposito
authors.affiliation: Q&T Research Incorporated, Sherbrooke, Québec, Canada.
authors.forename: Louise
authors.initials: L
authors.lastname: Frenette
authors.affiliation: Dipartimento di Pediatria, Azienda Ospedaliera Universitaria di Padova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
authors.affiliation: Canadian Center for Vaccinology, IWK Health Centre and NovaScotia Health Authority, Dalhousie University, Halifax.
authors.forename: Shelly
authors.initials: S
authors.lastname: McNeil
authors.affiliation: Medicor Research Inc, Sudbury, Ontario, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Rheault
authors.affiliation: Department of Health Sciences, School of Medical and Pharmaceutical Sciences, Vaccines and Clinical Trials Unit, IRCCS AOU San Martino-IST, University of Genoa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Durando
authors.affiliation: Pediatric Office Dr. med. Michael Horn, Bavaria.
authors.forename: Michael
authors.initials: M
authors.lastname: Horn
authors.affiliation: Department of Obstetrics and Gynecology, Freiburg Medical School, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Klar
authors.affiliation: GSK Vaccines, Rixensart.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Poncelet
authors.affiliation: GSK Vaccines, Rixensart.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: De Simoni
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Damien
authors.initials: D
authors.lastname: Friel
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: De Muynck
authors.affiliation: GSK Pharmaceuticals India Ltd., Bangalore, Karnataka, India.
authors.forename: Pemmaraju V
authors.initials: PV
authors.lastname: Suryakiran
authors.affiliation: Chiltern International for GSK, Wavre, Belgium.
authors.forename: Marjan
authors.initials: M
authors.lastname: Hezareh
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Descamps
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Thomas
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Struyf
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000367:Age Factors; D000536:Aluminum Hydroxide / Q000008:administration & dosage*; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives*; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C532963:ASO4 mixture; D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D008050:Lipid A; D053918:Papillomavirus Vaccines; D000536:Aluminum Hydroxide
keywords: 2-dose schedule; AS04; Adjuvant System containing 50 µg 3-O-desacyl-4′-monophosphoryl lipid A (MPL) adsorbed on aluminum salt (500 µg Al3+); CMI; GMT; HPV; IgG; cell-mediated immunity; cervical cancer; geometric mean antibody titer; human papillomavirus; immunogenicity