title: Immune response to the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose or 3-dose schedule up to 4 years after vaccination: results from a randomized study.
abstract: This randomized, partially-blind study (ClinicalTrials.gov registration number NCT00541970) evaluated the immunogenicity and safety of 2-dose (2D) schedules of the HPV-16/18 AS04-adjuvanted vaccine. Results to month (M) 24 have been reported previously and we now report data to M48 focusing on the licensed vaccine formulation (20 μg each of HPV-16 and -18 antigens) administered at M0,6 compared with the standard 3-dose (3D) schedule (M0,1,6). Healthy females (age stratified: 9-14, 15-19, 20-25 years) were randomized to receive 2D at M0,6 (n = 240) or 3D at M0,1,6 (n = 239). In the according-to-protocol immunogenicity cohort, all initially seronegative subjects seroconverted for HPV-16 and -18 antibodies and remained seropositive up to M48. For both HPV-16 and -18, geometric mean antibody titer (GMT) ratios (3D schedule in women aged 15-25 years divided by 2D schedule in girls aged 9-14 years) at M36 and M48 were close to 1, as they were at M7 when non-inferiority was demonstrated. The kinetics of HPV-16, -18, -31, and -45 antibody responses were similar for both groups and HPV-16 and -18 GMTs were substantially higher than natural infection titers. The vaccine had a clinically acceptable safety profile in both groups. In summary, antibody responses to a 2D M0,6 schedule of the licensed vaccine formulation in girls aged 9-14 years appeared comparable to the standard 3D schedule in women aged 15-25 years up to 4 years after first vaccination. A 2D schedule could facilitate implementation of HPV vaccination programs and improve vaccine coverage and series completion rates.
authors.affiliation: University of Alberta; Edmonton, AB Canada.
authors.forename: Barbara
authors.initials: B
authors.lastname: Romanowski
authors.affiliation: Central Laboratory and Vaccination Centre; Stiftung Juliusspital; Würzburg, Germany.
authors.forename: Tino F
authors.initials: TF
authors.lastname: Schwarz
authors.affiliation: Colchester Research Group; Truro, NS Canada.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Ferguson
authors.affiliation: Colchester Research Group; Truro, NS Canada.
authors.forename: Murdo
authors.initials: M
authors.lastname: Ferguson
authors.affiliation: Berner Heerweg 157; Hamburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Peters
authors.affiliation: Centre Hospitalier Universitaire; Québec, QC Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Dionne
authors.affiliation: Waisenhausstr. 52; Munich, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Schulze
authors.affiliation: First Line Medical Services Ltd.; St. John's, NL Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Ramjattan
authors.affiliation: Medizinische Hochschule Hannover; Hannover, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hillemanns
authors.affiliation: Hauptstrasse 240 Kehl Baden-Württemberg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Behre
authors.affiliation: GlaxoSmithKline; Bangalore, India.
authors.forename: Pemmaraju
authors.initials: P
authors.lastname: Suryakiran
authors.affiliation: GlaxoSmithKline Vaccines; Wavre, Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Thomas
authors.affiliation: GlaxoSmithKline Vaccines; Wavre, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Struyf
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D052162:Human papillomavirus 16 / Q000187:drug effects / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D013997:Time Factors; D014611:Vaccination / Q000639:trends*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D053918:Papillomavirus Vaccines
keywords: administration schedule; female adolescents; human papillomavirus vaccine; immunogenicity; randomized controlled trial; safety; women