Abstract
INTRODUCTION: Argentina was the first South American country to adopt a single-dose hepatitis A vaccine for 1-year-old children, replacing the standard two-dose regimen in the immunization program in 2005. Here, we assessed the long-term persistence of anti-hepatitis A virus (HAV) antibodies following vaccination. METHODS: A cohort of healthy toddlers from Mendoza, Argentina, who received one (N = 436) or two (N = 108) doses of the inactivated HAV vaccine (Avaxim(®) 80U Pediatric), were followed for up to 15 years post-vaccination to assess the persistence of anti-HAV antibodies. Three assays were used to measure anti-HAV antibody concentrations, depending on commercial availability. At year 15 follow-up, 161 and 48 participants who received one and two vaccine doses, respectively, without additional booster, remained in the study. Using all available data, we modeled long-term antibody persistence to project immunity to 40 years after vaccination. Antibody persistence was predicted using a hierarchical model that estimated both participant- and group-specific antibody decay, accounting for assay changes over time and natural boosting from virus exposure. RESULTS: At year 15, anti-HAV antibody geometric mean concentrations (GMCs) were 73.7 (95% CI 65.0-83.6) mIU/ml and 291.1 (95% CI 226.1-375.0) mIU/ml among those who received one and two vaccine doses, respectively, and all remained seroprotected. Of the four model specifications tested, the log-logistic model with natural boosting provided the best fit to the observed antibody GMCs and seroprotection rates. At 40 years post-vaccination, GMCs were predicted to be 51.8 (95% CI 36.8-75.1) mIU/ml and 134.7 (95% CI 84.5-221.1) mIU/ml after one and two vaccine doses, respectively, with seroprotection rates of 94% (95% CI 89-98) and 93% (95% CI 88-97). CONCLUSIONS: The HAV vaccine, Avaxim(®), administered as one- or two-dose schedule, elicited long-lasting immunity in children, with a single dose sufficient to ensure long-term protection.