Statistical modeling alongside observational data predicts long-term immunogenicity of one dose and two doses of pediatric hepatitis A vaccine in the Mendoza province of Argentina

Hepatitis A vaccination and its immunological and epidemiological long-term effects – a review of the evidence

“…64 In the second study, clinically insignificant 1.4-fold to moderate 3.4-fold rises in antibody levels were reported between some of the yearly visits in 17 of 142 children during a 3-year post-booster follow-up and were interpreted as "natural boosting"; 125 the follow-up serum samples were not tested in parallel at the end of the study (R. Dagan, personal communication). In the third study, 43,126,127 natural boosters were reported with yearly varying rates in up to one-third of Argentinian children during the 3-year, 126 during the 3-to 5-year 127 and finally at the 10-year follow-up, 43 in single-and 2-dose vaccinated children. The antibodies rose in the subjects concerned by only 80%-100% and the consecutive serum samples were not tested in parallel (C. Espul, personal communication).…”

“…The level of positive variations (≥25% increases) tended to decrease from Year 2 to Year 10, and there was no trend toward a relationship with hepatitis A cases in household members. 43 Likewise, it was in another study from Argentina reported that one-third of children from a long-term immunogenicity study had documented close contact (household, school, neighbors) with acute HA cases after immunization, but no significant difference was found between anti-HAV antibody levels in children reporting exposure and those reporting no contact with HA patients during 10 years. 128 All these reported "natural booster" cases are in our opinion wrongly labeled, as the very modest changes were most likely not genuine.…”

“…Real-time seroprotection following immunization with two doses (or three doses with lower antigen content than currently licensed) of inactivated monovalent HAV vaccines, or of a HAV antigen containing combined hepatitis A + B vaccine, has been investigated over ≥ 10 years in children (incl. infants & toddlers), [42][43][44][45][46][47][48][49][50][51][52][53] adolescents 54,55 and adults [56][57][58][59][60] (Table 2). These studies show quite consistently that healthy adults, as well as children and adolescents, will, following standard immunization schedules (0/6-12 months), be real-time seroprotected for up to 15-20 years in 95-100% of vaccinees, while mathematical modeling estimations extend this period up to 30-40 years in 84-97% of subjects.…”

“…[74][75][76] Argentina was the first country to introduce single-dose UMV in toddlers in 2005. 77 Immunogenicity data for inactivated HAV vaccines (all in young children) have currently reached 10 years of follow-up evaluations in a first study, 43 and the single-dose results are looking promising, with seroprotection rates of 100% (10 year follow-up), 43 95.2% (7.5 years), 31 97.4% (6.3-9.2 years), 78 92.9% (4 years), 79 and 85.9% (5 years) 80 (Table 3). Statistical modeling with 10 years of follow-up data resulted in a 30-year seroprotection (≥3 mIU/mL) for 89% of children after singledose vaccination.…”

“… a N = number of subjects at end of follow-up; b Age at vaccination: y = years, m = months; c Models used in the studies listed: piecewise linear model [Espul (2020) 43 ], log-linear model [Hammitt (2008) 57 ], mixed effects models [Lopez (2015) 44 ], fractional polynomial regression [Plumb (2017), 45 Mosites (2020) 53 ], random effects model [Spradling (2016) 50 ], linear mixed model [Wang (2020), 52 Chappuis (2017), 56 Theeten (2015), 59 Van Damme (2017) 60 ]; d Mosites (2018): 46 after 22 years of follow-up 16/16/14 subjects were seroprotected in 75%/94%/93% and had GMCs of 46/122/138 mIU/mL (no new modeling estimates); e ± maternal antibodies; f Estimate based on N = 127 → N = 7 (years 0 → 10) adult population; g Age at follow-up; h two separate phase IV studies with identical follow-up Abbreviations: GMC: geometric mean concentrations; nd: not done …”