Associations between serum metals and antibody levels against measles, rubella, and varicella vaccines in children with sex-specific nonlinear patterns

Abstract

Vaccination is a cornerstone of public health, protecting individuals from infectious diseases, contributing to herd immunity, reducing disease transmission, and safeguarding vulnerable populations. Despite the recognized importance of optimizing vaccine-induced immunity, the role of metal exposure in modulating antibody levels in children remains poorly understood. In this study, we assessed the associations between serum metal concentrations and antibody levels for measles, rubella, and varicella vaccines in 1076 children aged 3-12 years from Guangzhou, China. In multivariable linear regression analyses of the whole children, barium exhibited consistent negative associations with antibody levels for all three vaccines. In sex-stratified analyses, tin showed positive associations, whereas manganese showed negative associations with rubella antibody levels in both sexes. Additionally, barium was negatively associated with measles antibody levels in both sexes. In age-stratified analyses, zinc and tin were positively associated with rubella antibody levels, while manganese was negatively associated with rubella antibody levels in both age groups. Sex-stratified restricted cubic spline analyses revealed that a greater number of serum metals were significantly associated with varicella and rubella antibody levels in girls, whereas more metals were associated with measles antibody levels in boys. Specifically, serum lead and copper exhibited inverted U-shaped relationships with varicella antibody levels in girls, whereas aluminum, antimony, and iron showed complex nonlinear patterns with measles antibody levels in boys. Additionally, zinc demonstrated a positive threshold effect on rubella antibody levels in both sexes, whereas barium exhibited U-shaped associations with varicella and rubella antibody levels. There was a combined negative effect of metal mixtures on rubella antibody levels, with silver, manganese, and chromium identified as the main contributors. The results revealed that environmental metal exposure may influence vaccine-induced immunity in children, highlighting routine serum metal biomonitoring and potential interventions to ensure optimal vaccination effectiveness.

Keywords: Children; Humoral immunity; Metal exposure; Sex differences; Vaccine antibodies.