Cellular and humoral immunogenicity of a SARS-CoV-2 mRNA vaccine in patients on haemodialysis
Monika Strengert,
Matthias Becker,
Gema Morillas Ramos,
Alex Dulovic,
Jens Gruber,
Jennifer Juengling,
Karsten Lürken,
Andrea Beigel,
Eike Wrenger,
Gerhard Lonnemann,
Anne Cossmann,
Metodi V. Stankov,
Alexandra Dopfer-Jablonka,
Philipp D. Kaiser,
Bjoern Traenkle,
Ulrich Rothbauer,
Gérard Krause,
Nicole Schneiderhan-Marra,
Georg M.N. Behrens
Affiliations
Monika Strengert
Helmholtz Centre for Infection Research, Braunschweig, Germany; TWINCORE GmbH, Centre for Experimental and Clinical Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
Matthias Becker
NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
Gema Morillas Ramos
Department for Rheumatology and Immunology, Hannover Medical School, Hannover, Germany
Alex Dulovic
NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
Jens Gruber
NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
Jennifer Juengling
NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
Karsten Lürken
Dialysis Centre Eickenhof, Langenhagen, Germany
Andrea Beigel
Dialysis Centre Eickenhof, Langenhagen, Germany
Eike Wrenger
Dialysis Centre Eickenhof, Langenhagen, Germany
Gerhard Lonnemann
Dialysis Centre Eickenhof, Langenhagen, Germany
Anne Cossmann
Department for Rheumatology and Immunology, Hannover Medical School, Hannover, Germany
Metodi V. Stankov
Department for Rheumatology and Immunology, Hannover Medical School, Hannover, Germany
Alexandra Dopfer-Jablonka
Department for Rheumatology and Immunology, Hannover Medical School, Hannover, Germany; German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany
Philipp D. Kaiser
NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
Bjoern Traenkle
NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
Ulrich Rothbauer
NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany; Pharmaceutical Biotechnology, University of Tübingen, Germany
Gérard Krause
Helmholtz Centre for Infection Research, Braunschweig, Germany; TWINCORE GmbH, Centre for Experimental and Clinical Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
Nicole Schneiderhan-Marra
NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany; Corresponding author at: Nicole Schneiderhan-Marra, Marktwiesenstrasse 55, 72770 Reutlingen; Georg M.N. Behrens, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Georg M.N. Behrens
Department for Rheumatology and Immunology, Hannover Medical School, Hannover, Germany; German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany; CiiM - Centre for Individualized Infection Medicine, Hannover, Germany; Corresponding author at: Nicole Schneiderhan-Marra, Marktwiesenstrasse 55, 72770 Reutlingen; Georg M.N. Behrens, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Background: Patients with chronic renal insufficiency on maintenance haemodialysis face an increased risk of COVID-19 induced mortality and impaired vaccine responses. To date, only a few studies have 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 characterised 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 Alpha, Beta, Epsilon and Cluster 5 by ACE2-RBD competition assay. Findings: Patients on maintenance haemodialysis 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 a vaccinated non-dialysed control population. 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 maintenance haemodialysis are encouraging, but urge for longitudinal follow-up to assess longevity of immunity. Diminished virus neutralization and interferon γ responses in the face of emerging variants of concern may favour 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 Centres, EU Horizon 2020 research and innovation program, State Ministry of Baden-Württemberg for Economic Affairs, Labour and Tourism.
