Cellular and humoral immunogenicity of a SARS-CoV-2 mRNA vaccine in patients on hemodialysis
2021-05-29

Abstract Background Patients with chronic renal insufficiency on intermittent hemodialysis face an increased risk of COVID-19 induced mortality and impaired vaccine responses. To date, only few studies addressed SARS-CoV-2 vaccine elicited immunity in this immunocompromised population. Methods We assessed immunogenicity of the mRNA vaccine BNT162b2 in at risk dialysis patients and characterized systemic cellular and humoral immune responses in serum and saliva using interferon γ release assay and multiplex-based cytokine and immunoglobulin measurements. We further compared binding capacity and neutralization efficacy of vaccination-induced immunoglobulins against emerging SARS-CoV-2 variants of concern B.1.1.7, B.1.351, B.1.429 and Cluster 5 by ACE2-RBD competition assay. Findings Patients on intermittent hemodialysis exhibit detectable but variable cellular and humoral immune responses against SARS-CoV-2 and variants of concern after a two-dose regimen of BNT162b2. Although vaccination-induced immunoglobulins were detectable in saliva and plasma, both anti-SARS-CoV-2 IgG and neutralization efficacy was reduced compared to controls. Similarly, T-cell mediated interferon γ release after stimulation with SARS-CoV-2 spike peptides was significantly diminished. Interpretation Quantifiable humoral and cellular immune responses after BNT162b2 vaccination in individuals on intermittent dialysis are encouraging, but urge for longitudinal follow-up to assess longevity of immunity. Diminished virus neutralization and interferon γ responses in face of emerging variants of concern may favor this at risk population for re-vaccination using modified vaccines at the earliest opportunity. Funding Initiative and Networking Fund of the Helmholtz Association of German Research Centers, EU Horizon 2020 research and innovation program, State Ministry of Baden-Württemberg for Economic Affairs, Labor and Tourism. Research in the context Evidence before this study Patients on dialysis tend to have a reduced immune response to both infection and vaccination. We searched PubMed and MedRxiv for studies including search terms such as “COVID-19”, “vaccine”, and “dialysis” but no peer-reviewed studies to date assessed both SARS-CoV-2 specific B- and T-cell responses, mucosal immunoglobulins, and considered the impact of SARS-CoV-2 variants of concern in this at risk population. Added value of the study We provide a comprehensive functional characterization of both T- and B-cell responses following a two-dose regimen of BNT162b2 in at risk patients on maintenance hemodialysis. More importantly, to the best of our knowledge, we assess for the first time binding and neutralization capacity of vaccination-induced circulation and mucosal antibodies towards emerging SARS-CoV-2 variants of concern in an immunocompromised population. Implications of all the available evidence Patients on maintenance hemodialysis develop a substantial cellular and humoral immune response following the BNT162b2 vaccine. These findings should encourage patients on intermittent hemodialysis to receive the vaccine. However, we suggest continuing additional protection measures against variants of concern in this at risk population until longevity of the vaccine response is fully evaluated.