Date Published: October 10, 2018
Publisher: Public Library of Science
Author(s): Elizabeth N. da Silva, Alan Baker, Jalila Alshekaili, Krishna Karpe, Matthew C. Cook, Joseph J. Mattapallil.
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.
We studied serological and cellular responses to HBV in CKD to identify a defect in vaccine-induced 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).
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 non-responders. 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.
CKD confers a specific T cell defect that contributes to the impaired seroconversion to HBV.
End-stage renal disease confers a state of chronic immune deficiency, which results in poor response to standard vaccination regimens, and increased risk of infection, including chronic viral infections that can increase risk of cancer . The risk of hepatitis B virus infection is particularly significant due to increased exposure to the virus during dialysis, and an increased risk of chronic infection and mortality . Current guidelines recommend routine vaccination of dialysis patients with three or four 40mcg doses of hepatitis B vaccine (HBV), however, there is no universal dosing recommendation for pre-dialysis CKD patients [2–4]. The Centers for Disease Control and Prevention recommends 20mcg of HBV intramuscularly at 0, 1, 6 months in pre-dialysis patients. A significant proportion of CKD patients vaccinated prior to the commencement of dialysis remain at risk of contracting hepatitis B virus due to impaired seroconversion and rapid decline of protective titers . Several studies have sought to address the possible benefit of augmenting the pre-dialysis schedule to four 40mg doses, however the data are so far inconclusive [5–7].
End stage renal disease appears to be a state of immune deficiency [1,11,32], with increased risk of infection and of viral infection-related cancer . Detailed information regarding the immune defects conferred by CKD has been difficult to obtain. We characterized memory and effector T and B cell compartments in CKD and examined how these lymphocyte populations respond to vaccination. We observed that a higher proportion of CXCR3+ cTFH at baseline is associated with a more robust response to vaccination, and that activation of this subset of cTFH correlated with vaccine response. At baseline, CKD patients are relatively deficient in the CXCR3+ cTFH subset (Fig 4B), and this is more pronounced in serological non-responders to HBV vaccination (Fig 4C).