A randomized trial of serological and cellular responses to hepatitis B vaccination in chronic kidney disease

Background Chronic kidney disease (CKD) is associated with an increased risk of hepatitis B infection and impaired seroconversion to hepatitis B vaccine (HBV). Studies examining augmented vaccine schedules to enhance seroconversion have so far been inconclusive. Furthermore, the defects responsible for impaired vaccine immunity in CKD have not yet been identified. Methods We studied serological and cellular responses to HBV in CKD to identify a defect in vaccineinduced cellular responses that could account for impaired seroconversion in CKD and clarify the effects of an augmented vaccine dose schedule. We compared these results with responses to seasonal influenza vaccination (Fluvax). Results We found a clear benefit in rates and magnitude of seroconversion after an augmented 40mcg HBV dose schedule in CKD. This permitted comparison of responders and nonresponders. Serological non-responders with CKD exhibited reduction in CXCR3+CCR6- CXCR5+ memory T cells at baseline. Unlike Fluvax, HBV elicited a poor plasmablast (PB) response. Both vaccinations induced activation of the CXCR3+CCR6- CCR7- subset of circulating T follicular helper cells (cTFH), although this response was impaired in CKD after HBV. Conclusions CKD confers a specific T cell defect that contributes to the impaired seroconversion to HBV.