title: Sustained immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine administered as a two-dose schedule in adolescent girls: Five-year clinical data and modeling predictions from a randomized study.
abstract: In this randomized, partially-blind study ( clinicaltrials.gov ; NCT00541970), the licensed formulation of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (20 μg each of HPV-16/18 antigens) was found highly immunogenic up to 4 y after first vaccination, whether administered as a 2-dose (2D) schedule in girls 9-14 y or 3-dose (3D) schedule in women 15-25 y. This end-of-study analysis extends immunogenicity and safety data until Month (M) 60, and presents antibody persistence predictions estimated by piecewise and modified power law models. Healthy females (age stratified: 9-14, 15-19, 20-25 y) were randomized to receive 2D at M0,6 (N = 240 ) or 3D at M0,1,6 (N = 239). Here, results are reported for girls 9-14 y (2D) and women 15-25 y (3D). Seropositivity rates, geometric mean titers (by enzyme-linked immunosorbent assay) and geometric mean titer ratios (GMRs; 3D/2D; post-hoc exploratory analysis) were calculated. All subjects seronegative pre-vaccination in the according-to-protocol immunogenicity cohort were seropositive for anti-HPV-16 and -18 at M60. Antibody responses elicited by the 2D and 3D schedules were comparable at M60, with GMRs close to 1 (anti-HPV-16: 1.13 [95% confidence interval: 0.82-1.54]; anti-HPV-18: 1.06 [0.74-1.51]). Statistical modeling predicted that in 95% of subjects, antibodies induced by 2D and 3D schedules could persist above natural infection levels for ≥ 21 y post-vaccination. The vaccine had a clinically acceptable safety profile in both groups. In conclusion, a 2D M0,6 schedule of the HPV-16/18 AS04-adjuvanted vaccine was immunogenic for up to 5 y in 9-14 y-old girls. Statistical modeling predicted that 2D-induced antibodies could persist for longer than 20 y.
authors.affiliation: a University of Alberta ; Edmonton , AB , Canada.
authors.forename: Barbara
authors.initials: B
authors.lastname: Romanowski
authors.affiliation: b Central Laboratory and Vaccination Center; Stiftung Juliusspital ; Würzburg , Germany.
authors.forename: Tino F
authors.initials: TF
authors.lastname: Schwarz
authors.affiliation: c Colchester Research Group ; Truro , NS , Canada.
authors.forename: Linda
authors.initials: L
authors.lastname: Ferguson
authors.affiliation: d Berner Heerweg 157 ; Hamburg , Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Peters
authors.affiliation: e Centre Hospitalier Universitaire ; Québec , QC , Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Dionne
authors.affiliation: f Hauptstrasse 240; Kehl Baden-Württemberg ; Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Behre
authors.affiliation: g Waisenhausstrasse 52 ; Munich , Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Schulze
authors.affiliation: h Medizinische Hochschule Hannover ; Hannover , Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hillemanns
authors.affiliation: i GlaxoSmithKline ; Bangalore , India.
authors.forename: Pemmaraju
authors.initials: P
authors.lastname: Suryakiran
authors.affiliation: j GSK Vaccines ; Wavre , Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Thomas
authors.affiliation: j GSK Vaccines ; Wavre , Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Struyf
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000536:Aluminum Hydroxide / Q000008:administration & dosage* / Q000009:adverse effects; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; 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 / Q000009:adverse effects / Q000031:analogs & derivatives*; D030361:Papillomavirus Infections / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C532963:ASO4 mixture; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D008050:Lipid A; D053918:Papillomavirus Vaccines; D000536:Aluminum Hydroxide
keywords: administration schedule; female adolescents; human papillomavirus vaccine; immunogenicity; randomized controlled trial; safety; women