Long-Term Persistence of Antibody Response with Two Doses of Inactivated Hepatitis A Vaccine in Children

Ashish Agrawal, Shafi Kolhapure, Anar Andani, Martin O C Ota, Selim Badur, Naveen Karkada, Monjori Mitra, Ashish Agrawal, Shafi Kolhapure, Anar Andani, Martin O C Ota, Selim Badur, Naveen Karkada, Monjori Mitra

Abstract

Introduction: Hepatitis A virus infection is more severe in adults than children. Although vaccination can protect adults, current childhood programs cover a large population more successfully. Childhood vaccination is, therefore, a solution to protecting adults if it induces lasting immunity. Fifteen-year protection has been demonstrated in children, but longer-term data are only available for adults. We aimed to predict long term persistence of antibody in children beyond 15 years and assess if immunological mechanisms triggered by vaccination support longer-term protection.

Methods: Long-term clinical studies using hepatitis A (HAV) or A/B vaccines (HAB) containing 720 or 1440 Enzyme-linked immunosorbent assay Units (EU) of hepatitis A virus antigen were identified. Duration of persistence of antibodies and possible protection was determined by descriptively comparing antibody geometric mean concentration (GMC) kinetics, as well as GMC (95% confidence interval) at 15 years post-vaccination across studies. Immunological mechanism studies describing hepatitis A vaccination were identified.

Results: One study in children 12-15 years (2-dose HAB 720) and four in adults (2-dose HAV 1440 and 3-dose HAB 720) showed comparable GMC kinetics and per year rates of change up to 15 years. At 15 years, the GMC in children [414.7 mEU/ml (336.9; 510.5)] was in the same range as in adults [range 282.6 (217.6; 367.0) to 550.1 (416.0; 727.4)]. Based on these data, mathematical model predictions from adult studies (showing > 85% protected at 50 years) were deemed likely to also apply to children. Studies identified, both humoral and cell-mediated responses are induced following vaccination.

Conclusion: Based on comparable antibody data in adults and children up to 15 years, similar longer-term antibody persistence is expected in children with 2-dose inactivated hepatitis A 720 containing vaccine at least up to 50 years. Accordingly, improving routine childhood hepatitis A vaccination coverage could protect against more severe disease in adulthood. Fig. 1 Plain language summary TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT00875485, NCT01000324, NCT01037114, NCT00289757, NCT00291876.

Keywords: Children; Inactivated hepatitis A vaccine; Long-term persistence.

Figures

Fig. 1
Fig. 1
Plain language summary
Fig. 2
Fig. 2
Antibody geometric mean concentration by study (TVC cohort). There was a change in the assay used during follow-up (year 6 and year 11 for 3-dose and 2-dose adult studies, respectively). The cut-off used in the new assay differed, as seen by the peak in the graphs for these years. GMC geometric mean concentration, EU enzyme-linked immunosorbent assay units, HAB combination hepatitis A and B virus vaccine, HAV hepatitis A virus vaccine, TVC total vaccinated cohort
Fig. 3
Fig. 3
Antibody geometric mean concentration fold change by study (TVC cohort). There was a change in the assay used during follow-up (year 6 and year 11 for 3-dose and 2-dose adult studies, respectively). The cut-off used in the new assay differed, as seen by the peak in the graphs for these years. GMC geometric mean concentration (enzyme-linked immunosorbent assay units), HAB combination hepatitis A and B virus vaccine, HAV hepatitis A virus vaccine, TVC total vaccinated cohort

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