title: 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.
abstract: 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.
authors: University of Alberta, Edmonton, AB, Canada. broman@docromanowski.com
authors: Barbara
authors: B
authors: Romanowski
authors: Tino F
authors: TF
authors: Schwarz
authors: Linda M
authors: LM
authors: Ferguson
authors: Klaus
authors: K
authors: Peters
authors: Marc
authors: M
authors: Dionne
authors: Karin
authors: K
authors: Schulze
authors: Brian
authors: B
authors: Ramjattan
authors: Peter
authors: P
authors: Hillemanns
authors: Grégory
authors: G
authors: Catteau
authors: Kurt
authors: K
authors: Dobbelaere
authors: Anne
authors: A
authors: Schuind
authors: Dominique
authors: D
authors: Descamps
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects*; D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology; D052161:Human papillomavirus 18 / Q000276:immunology; D006801:Humans; D008004:Licensure; D008050:Lipid A / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000276:immunology; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D055815:Young Adult
chemical_list: C532963:ASO4 mixture; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D008050:Lipid A; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18; D000536:Aluminum Hydroxide