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.

Conclusion: This analysis, using previously used and newly selected model structures, was consistent with former estimates of seropositivity rates ≥95% for at least 25 years.

Keywords: Changepoint model; Immunogenicity assay; Long term follow-up; Longitudinal data analysis; Vaccine trials.