title: Model based estimates of long-term persistence of inactivated hepatitis A vaccine-induced antibodies in adults.
abstract: BACKGROUND
  In this paper, we review the results of existing statistical models of the long-term persistence of hepatitis A vaccine-induced antibodies in light of recently available immunogenicity data from 2 clinical trials (up to 17 years of follow-up).
  
  
  METHODS
  Healthy adult volunteers monitored annually for 17 years after the administration of the first vaccine dose in 2 double-blind, randomized clinical trials were included in this analysis. Vaccination in these studies was administered according to a 2-dose vaccination schedule: 0, 12 months in study A and 0, 6 months in study B (NCT00289757/NCT00291876). Antibodies were measured using an in-house ELISA during the first 11 years of follow-up; a commercially available ELISA was then used up to Year 17 of follow-up. Long-term antibody persistence from studies A and B was estimated using statistical models for longitudinal data. Data from studies A and B were modeled separately.
  
  
  RESULTS
  A total of 173 participants in study A and 108 participants in study B were included in the analysis. A linear mixed model with 2 changepoints allowed all available results to be accounted for. Predictions based on this model indicated that 98% (95%CI: 94-100%) of participants in study A and 97% (95%CI: 94-100%) of participants in study B will remain seropositive 25 years after receiving the first vaccine dose. Other models using part of the data provided consistent results: ≥95% of the participants was projected to remain seropositive for ≥25 years.
  
  
  CONCLUSIONS
  This analysis, using previously used and newly selected model structures, was consistent with former estimates of seropositivity rates ≥95% for at least 25 years.
authors: Centre for Health Economic Research and Modeling Infectious Diseases (CHERMID), Vaccine & Infectious Disease Institute (WHO Collaborating Centre), University of Antwerp, Wilrijk, Belgium; Center for Statistics (CenStat), Interuniversity Institute of Biostatistics and statistical Bioinformatics (I-BioStat), Hasselt University, Diepenbeek, Belgium.
authors: Niel
authors: N
authors: Hens
authors: Center for Statistics (CenStat), Interuniversity Institute of Biostatistics and statistical Bioinformatics (I-BioStat), Hasselt University, Diepenbeek, Belgium.
authors: Aklilu
authors: A
authors: Habteab Ghebretinsae
authors: GlaxoSmithKline Vaccines, Wavre, Belgium.
authors: Karin
authors: K
authors: Hardt
authors: Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (WHO Collaborating Centre), University of Antwerp, Wilrijk, Belgium. Electronic address: pierre.vandamme@ua.ac.be.
authors: Pierre
authors: P
authors: Van Damme
authors: Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (WHO Collaborating Centre), University of Antwerp, Wilrijk, Belgium; Department of Public Health, Ghent University, Ghent, Belgium.
authors: Koen
authors: K
authors: Van Herck
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation; D005260:Female; D005500:Follow-Up Studies; D006506:Hepatitis A / Q000517:prevention & control; D035922:Hepatitis A Antibodies / Q000097:blood*; D022362:Hepatitis A Vaccines / Q000627:therapeutic use*; D006801:Humans; D007117:Immunization, Secondary; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D015164:Vaccines, Inactivated / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D035922:Hepatitis A Antibodies; D022362:Hepatitis A Vaccines; D015164:Vaccines, Inactivated
keywords: Changepoint model; Immunogenicity assay; Long term follow-up; Longitudinal data analysis; Vaccine trials