- D3.530 - Nonresponsiveness to Hepatitis B Vaccine Is Characterized by Reduced T Stem Cell Memory (TSCM) Cells

Although hepatitis B vaccination is highly effective, a subset of vaccinated individuals fails to develop protective antibody levels and is classified as nonresponders. Long-term protection against hepatitis B relies not only on humoral immunity but also on durable cellular immune memory. Among memory T cell subsets, T stem cell memory (TSCM) cells possess self-renewal capacity and contribute to sustained immune responses. However, their role in hepatitis B vaccine responsiveness remains insufficiently characterized. This study investigated whether differences in CD4⁺ memory T cell subsets, particularly TSCM cells, are associated with nonresponsiveness to hepatitis B vaccination.

Healthcare workers vaccinated against hepatitis B were enrolled and categorized as responders (anti-HBs antibody >100 mIU/mL, n=13) or nonresponders (anti-HBs antibody <10 mIU/mL after at least two full vaccination series, n=15). Peripheral blood mononuclear cells were isolated and stimulated in vitro with hepatitis B surface antigen and phytohemagglutinin. CD4⁺ memory T cell subsets were identified using multiparameter flow cytometry based on CCR7, CD45RO, and CD95 expression. In parallel, intracellular interferon-gamma (IFN-γ) production by memory T cells was assessed. Statistical comparisons were performed using nonparametric analyses.

Nonresponders exhibited a significantly lower frequency of CD4⁺ TSCM cells, including total CD95⁺, CD95^high, and CD95^low/medium TSCM subsets, compared with responders. In contrast, no significant differences were observed between groups in other CD4⁺ memory T cell populations, such as naïve, central memory, or effector memory T cells. Additionally, the frequency and mean expression of IFN-γ–producing CD4⁺ memory T cells did not differ significantly between responders and nonresponders.

These findings suggest that failure to respond to hepatitis B vaccination is associated with impaired formation of CD4⁺ T stem cell memory cells rather than defects in cytokine production or other memory T cell subsets. Reduced TSCM frequency may contribute to insufficient long-term immune memory and poor antibody responses in nonresponders. Strategies aimed at enhancing TSCM generation may improve vaccine efficacy in this population.