title: Long-term immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in 10- to 14-year-old girls: open 6-year follow-up of an initial observer-blinded, randomized trial.
abstract: BACKGROUND
  Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine were evaluated up to 6 years postvaccination (month 72) in preteen/adolescent girls.
  
  
  METHODS
  Participants, who had received 3 HPV-16/18 AS04-adjuvanted vaccine doses at 10-14 years of age in an initial controlled, observer-blinded, randomized study (NCT00196924) and participated in the open 3-year follow-up (NCT00316706), were invited to continue the follow-up for up to 10 years postvaccination (NCT00877877). Anti-HPV-16 and -18 antibody titers were measured by enzyme-linked immunosorbent assays at yearly visits and were used to fit the modified power-law and piecewise models, predicting long-term immunogenicity. Serious adverse events (SAEs) and pregnancy information were recorded.
  
  
  RESULTS
  In the according-to-protocol immunogenicity cohort, all participants (N = 505) with data available remained seropositive for anti-HPV-16 and -18 antibodies at month 72. In initially seronegative participants, anti-HPV-16 and -18 antibody geometric mean titers were 65.8- and 33.0-fold higher than those associated with natural infection (NCT00122681) and 5.0- and 2.5-fold higher than those measured at month 69-74 in a study demonstrating vaccine efficacy in women aged 15-25 years (NCT00120848). Exploratory antibody modeling, based on the 6-year data, predicted that vaccine-induced population anti-HPV-16 and -18 antibody geometric mean titers would remain above those associated with natural infection for at least 20 years postvaccination. The HPV-16/18 AS04-adjuvanted vaccine safety profile was clinically acceptable.
  
  
  CONCLUSIONS
  In preteen/adolescent girls, the HPV-16/18 AS04-adjuvanted vaccine induced high anti-HPV-16 and -18 antibody levels up to 6 years postvaccination, which were predicted to remain above those induced by natural infection for at least 20 years.
authors: From the *Central Laboratory and Vaccination Centre, Stiftung Juliusspital Wuerzburg, Wuerzburg, Germany; †National Taiwan University Hospital, Taipei, Taiwan; ‡Chang Gung Memorial Hospital, Chang Gung Children's Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan; §Praxis für Kinder- und Jugendmedizin, Weilheim i.OB, Germany; ¶Gemeinschaftspraxis für Kinder- und Jugendmedizin, Mannheim, Germany; ‖Fundación Santa Fe de Bogotá, Bogota, Colombia; **GlaxoSmithKline Vaccines, Bangalore, India; ††XPE Pharma and Science, Wavre, Belgium on behalf of GlaxoSmithKline Vaccines; and §§GlaxoSmithKline Vaccines, Wavre, Belgium.
authors: Tino F
authors: TF
authors: Schwarz
authors: Li-Min
authors: LM
authors: Huang
authors: Tzou-Yien
authors: TY
authors: Lin
authors: Christoph
authors: C
authors: Wittermann
authors: Falko
authors: F
authors: Panzer
authors: Alejandra
authors: A
authors: Valencia
authors: Pemmaraju V
authors: PV
authors: Suryakiran
authors: Lan
authors: L
authors: Lin
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*; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D008050:Lipid A / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D011247:Pregnancy; D016037:Single-Blind Method; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control; 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