Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose schedule compared with the licensed 3-dose schedule: results from a randomized study

Hum Vaccin. 2011 Dec;7(12):1374-86. doi: 10.4161/hv.7.12.18322. Epub 2011 Dec 1.


The immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix®, GlaxoSmithKline Biologicals) administered according to its licensed vaccination schedule (3-dose, 3D) and formulation (20 μg of each HPV antigen; 20/20F) has previously been demonstrated. This partially-blind, controlled, randomized trial (NCT00541970) evaluated 2-dose (2D) schedules using the licensed 20/20F or an alternative formulation containing 40 μg of each antigen (40/40F), compared with the licensed 3D schedule. Healthy females stratified by age (9-14, 15-19, 20-25 y) were randomized to receive 2 doses of 20/20F at Months (M) 0,6 (n=240), 40/40F at M0,6 (n=241) or 40/40F at M0,2 (n=240), or 3 doses of 20/20F at M0,1,6 (licensed schedule/formulation, n=239). One month after the last dose, the 3D schedule was not immunologically superior to 2D schedules except in the 40/40F M0,2 group for HPV-16 (lower limit of 95% CI geometric mean antibody titer (GMT) ratio [2D/3D] < 0.5). For both HPV-16 and HPV-18, the 2D schedules in girls 9-14 y were immunologically non-inferior to the 3D schedule in women 15-25 y (the age group in which efficacy has been demonstrated) (upper limit of 95% CI for GMT ratio [3D/2D] < 2) one month after the last dose. At Month 24, non-inferiority was maintained for the 2D M0,6 schedules in girls 9-14 y versus the 3D schedule in women 15-25 y. All formulations had acceptable reactogenicity and safety profiles. These results indicate that the HPV-16/18 vaccine on a 2D M0,6 schedule is immunogenic and generally well tolerated in girls 9-14 y and that the 2D schedule is likely adequate for younger females.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / adverse effects*
  • Adolescent
  • Adult
  • Aluminum Hydroxide / administration & dosage
  • Aluminum Hydroxide / adverse effects*
  • Aluminum Hydroxide / immunology*
  • Antibodies, Viral / blood*
  • Child
  • Dose-Response Relationship, Immunologic
  • Drug Administration Schedule
  • Female
  • Human papillomavirus 16 / immunology
  • Human papillomavirus 18 / immunology
  • Humans
  • Licensure
  • Lipid A / administration & dosage
  • Lipid A / adverse effects
  • Lipid A / analogs & derivatives*
  • Lipid A / immunology
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines / administration & dosage
  • Papillomavirus Vaccines / adverse effects*
  • Papillomavirus Vaccines / immunology*
  • Treatment Outcome
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / prevention & control*
  • Uterine Cervical Neoplasms / virology
  • Young Adult


  • ASO4 mixture
  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Lipid A
  • Papillomavirus Vaccines
  • human papillomavirus vaccine, L1 type 16, 18
  • Aluminum Hydroxide

Associated data