Hepatitis B vaccine immunity in healthcare workers: Seroprotection and cellular immune signatures of waning response.

Abstract

Hepatitis B virus (HBV) poses a significant occupational hazard for healthcare workers (HCWs), particularly in low and middle-income countries with limited routine postvaccination surveillance. While primary vaccination confers robust protection, immunity may wane over time, and the immunological mechanisms underlying nonresponsiveness remain poorly defined. We conducted a cross-sectional study among 119 HCWs at a tertiary care biomedical research institute in India. Participants completed structured questionnaires on HBV vaccination history and underwent serological testing for hepatitis B surface antibodies (anti-HBs). Titers ≥10 mIU/mL were considered protective. A representative subset (<i>n</i> = 6) underwent immunophenotyping by multicolor flow cytometry to characterize memory B cells, CD4⁺/CD8⁺ T cell subsets, and natural killer (NK) cells. Associations between seroprotection and demographic or occupational variables were assessed using logistic regression. Among 113 HCWs tested, 61.1% had protective anti-HBs titers. Recent vaccination (<5 years) was strongly associated with seroprotection (OR 9.99, 95% CI 3.45-28.92, <i>P</i> < 0.001), while vaccination 5-10 years prior showed a moderate association (OR 5.20, 95% CI 1.16-23.31, <i>P</i> = 0.031). Immunophenotyping revealed higher NK cell and class-switched memory B cell frequencies among responders compared to nonresponders, who exhibited skewed B cell maturation and reduced effector memory T cell populations. Durability of HBV vaccine-induced immunity among HCWs is suboptimal beyond 10 years, with immunophenotypic signatures suggesting cellular correlates of nonresponsiveness. These findings support routine serological monitoring and consideration of booster strategies tailored to immune profile in high-risk occupational groups.