Pediatric Vaccine-Induced Antibody Thresholds: Rethinking Pre-Immunosuppression Serologic Testing and Revaccination Implications

Abstract

Background Immune response to vaccination is assessed when adequate vaccine protection is in question or immunosuppression is imminent through measurement of antibody levels, which wane as time from vaccination increases. The serologic cutoff value for adequate response is based on thresholds derived from studies in adults, and age-appropriate thresholds for children have not been established. We sought to investigate age-specific differences in antibody levels in healthy children to guide determination of vaccine immunity status when clinically indicated. Methods This cross-sectional study assessed clinical serology for measles, mumps, rubella (MMR), varicella, and hepatitis B (HepB) in an age-stratified cohort of 471 healthy children who were up to date for vaccination (1 to 18 years). Remnant specimens with sufficient volume were collected from July 23, 2019, to November 17, 2020, as convenience samples and chart reviewed for inclusion. Results While children of all ages had detectable titers to MMR, median titers for HepB and varicella waned by ages 11 to 12 and 9 to 10 years, respectively. Children had titers above adult thresholds for MMR at all measured timepoints, retrospectively resulting in 24.6% (95% CI, 21.6%–27.8%) of children having an inappropriate MMR classification when adult instead of pediatric thresholds were used. Current use of HepB and varicella serology may be inappropriate due to the rapid waning of titers. The adequacy of an individual’s response to one vaccine component did not infer adequate responses to other components. Conclusions Application of age-appropriate reference intervals for vaccine serologic tests will provide a foundation for improved treatment recommendations and standards of care.