title: Long-term persistence of anti-HPV-16 and -18 antibodies induced by vaccination with the AS04-adjuvanted cervical cancer vaccine: modeling of sustained antibody responses.
abstract: OBJECTIVE
  Strong and sustained HPV-16 and -18 antibody responses have been observed in previously unexposed women aged 15-25 years vaccinated with the AS04-adjuvanted HPV-16/18 L1 virus-like particle vaccine. While awaiting the extended results of ongoing trials, our objective was to predict the long-term persistence of anti-HPV-16/18 antibodies in vaccinees by applying three statistical models using immunogenicity data from vaccinated women with serum samples collected up to 6.4 years after first vaccination. Two different data lock-points (up to 5.5 years and up to 6.4 years) were used to assess the robustness of the models.
  
  
  METHODS
  Three statistical models were applied to estimate the long-term persistence of anti-HPV-16/18 antibodies in 393 women vaccinated with the AS04-adjuvanted HPV-16/18 vaccine. Individual antibody levels for each study participant at each timepoint up to 6.4 years were input to previously published power-law and modified power-law models. The power-law model estimates antibody decay over time. The modified power-law model takes into account both antibody persistence over time and immune memory. A third model, the piece-wise model, fits the data based on three different non-overlapping intervals (between Months 7 and 12, Months 12 and 21, and over 21 months), corresponding to the observed decay of vaccine-induced antibodies.
  
  
  RESULTS
  HPV-16 and -18 antibodies peaked at Month 7 and gradually plateaued at Months 18-24 and remained stable through 6.4 years. Mean antibody levels at the last timepoint were several fold higher than those associated with natural infection. All three models predict that HPV-16 and -18 mean antibody levels will remain well above those associated with natural infection for at least 20 years, when using data from 5.5 as well as 6.4 years' follow-up. Predictions are similar for the modified power-law model and improve with longer follow-up for both the power-law and the piece-wise models.
  
  
  CONCLUSIONS
  Vaccination with the AS04-adjuvanted HPV-16/18 vaccine is predicted to provide long-term persistence for both HPV-16 and -18 antibodies, independent of the statistical model applied. Model predictions are based on conservative mathematical assumptions. Since the input of longer term data of up to 6.4 years showed an improved profile compared with that for data up to 5.5 years, the predictions of antibody persistence based on population means are conservative when predicting that antibody levels will remain well above levels induced by natural infection for 20 years.
authors.affiliation: GlaxoSmithKline Biologicals, B-1330, Rixensart, Belgium. marie-pierre.david@gskbio.com
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: David
authors.forename: Koen
authors.initials: K
authors.lastname: Van Herck
authors.forename: Karin
authors.initials: K
authors.lastname: Hardt
authors.forename: Fabian
authors.initials: F
authors.lastname: Tibaldi
authors.forename: Gary
authors.initials: G
authors.lastname: Dubin
authors.forename: Dominique
authors.initials: D
authors.lastname: Descamps
authors.forename: Pierre
authors.initials: P
authors.lastname: Van Damme
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D000917:Antibody Formation; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000276:immunology*; D006801:Humans; D015233:Models, Statistical; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D019496:Cancer Vaccines; D053918:Papillomavirus Vaccines