Long-term immunity and IgG subclass response following Hepatitis E vaccination: A longitudinal cohort study in Matlab, Bangladesh

OBJECTIVE: To assess long-term humoral and cellular immunity, including IgG subclass-specific responses, 24-35 months after HEV 239 (Hecolin®) vaccination among women in an HEV-endemic region. METHODS: A longitudinal cohort study was conducted in Matlab, Bangladesh, enrolling 1480 women (16-39 years) from a prior phase 4 cluster-randomized trial. Participants were categorized into four groups based on baseline serostatus and vaccine type: two HEV-vaccinated groups (seronegative and seropositive at baseline) and two HBV-vaccinated control groups. HEV IgG and IgG subclasses were measured, and limited ELISPOT assays assessed IFN-γ and IL-4 responses. Follow-up occurred 24-35 months post-vaccination. RESULTS: After two years, seropositivity remained significantly higher in the HEV-vaccinated participants (83.7%) than in HBV controls (51.6%, P < 0.001), indicating durable immunity. Vaccinated participants showed IgG4 and IgG2 dominance, whereas controls demonstrated predominantly IgG2 responses, consistent with natural infection. ELISPOT assays revealed persistent IFN-γ and IL-4 production, suggesting Th1-polarized cellular memory, though interpretation was limited by low PBMC recovery. CONCLUSION: This research reveals the first long-term IgG subclass-specific and cellular immunity data following HEV 239 vaccination in an endemic population. The findings demonstrate durable immune responses and offer crucial evidence to inform future HEV vaccination strategies for endemic regions like Bangladesh.