title: Persistence of immune responses to the HPV-16/18 AS04-adjuvanted vaccine in women aged 15-55 years and first-time modelling of antibody responses in mature women: results from an open-label 6-year follow-up study.
abstract: OBJECTIVE
  Evaluation of the long-term HPV-16/18 AS04-adjuvanted vaccine immunogenicity persistence in women.
  
  
  METHODS
  Multicentre, open-label, long-term follow-up (NCT00947115) of a primary phase-III study (NCT00196937).
  
  
  METHODS
  Six centres in Germany and Poland.
  
  
  METHODS
  488 healthy women (aged 15-55 years, age-stratified into groups: 15-25, 26-45, and 46-55 years) who received three vaccine doses in the primary study.
  
  
  METHODS
  Immune responses were evaluated in serum and cervicovaginal secretion (CVS) samples 6 years after dose 1. Anti-HPV-16/18 geometric mean titres (GMTs) were measured by enzyme-linked immunosorbent assay (ELISA), and were used to fit the modified power-law and piecewise models, predicting long-term immunogenicity. Serious adverse events (SAEs) were recorded.
  
  
  METHODS
  Anti-HPV-16/18 seropositivity rates and GMTs 6 years after dose 1.
  
  
  RESULTS
  At 6 years after dose 1, all women were seropositive for anti-HPV-16 and ≥97% were seropositive for anti-HPV-18 antibodies. GMTs ranged from 277.7 to 1344.6 EU/ml, and from 97.6 to 438.2 EU/ml, for anti-HPV-16 and anti-HPV-18, respectively. In all age groups, GMTs were higher (anti-HPV-16, 9.3-45.1-fold; anti-HPV-18, 4.3-19.4-fold) than levels associated with natural infection (29.8 EU/ml). A strong correlation between serum and CVS anti-HPV-16/18 levels was observed, with correlation coefficients of 0.81-0.96 (anti-HPV-16) and 0.69-0.84 (anti-HPV-18). Exploratory modelling based on the 6-year data predicted vaccine-induced anti-HPV-16/18 levels above natural infection levels for at least 20 years, except for anti-HPV-18 in the older age group (piecewise model). One vaccine-related and two fatal SAEs were reported.
  
  
  CONCLUSIONS
  At 6 years after vaccination, immune responses induced by the HPV-16/18 AS04-adjuvanted vaccine were sustained in all age groups.
authors.affiliation: Central Laboratory and Vaccination Centre, Stiftung Juliusspital, Würzburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Schwarz
authors.forename: M
authors.initials: M
authors.lastname: Spaczynski
authors.forename: A
authors.initials: A
authors.lastname: Kaufmann
authors.forename: J
authors.initials: J
authors.lastname: Wysocki
authors.forename: A
authors.initials: A
authors.lastname: Gałaj
authors.forename: K
authors.initials: K
authors.lastname: Schulze
authors.forename: P
authors.initials: P
authors.lastname: Suryakiran
authors.forename: F
authors.initials: F
authors.lastname: Thomas
authors.forename: D
authors.initials: D
authors.lastname: Descamps
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D052162:Human papillomavirus 16 / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000276:immunology* / Q000627:therapeutic use; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18
keywords: HPV-16/18 AS04-adjuvanted vaccine; human papillomavirus; persistence