A third vaccine dose substantially improves humoral and cellular SARS-CoV-2 immunity in renal transplant recipients with primary humoral nonresponse
Authors: Timm H. Westhoff, Felix S. Seibert, Moritz Anft, Arturo Blazquez-Navarro, Sarah Skrzypczyk, Panagiota Zgoura, Toni L. Meister, Stephanie Pfaender, Julian Stumpf, Christian Hugo, Richard Viebahn, Toralf Roch, Ulrik Stervbo, Nina Babel
Journal: Kidney International (2021)

Renal transplant recipients (RTRs) are at a high risk for fatal coronavirus disease 2019 (COVID-19).1ERA-EDTA Council; ERACODA Working GroupChronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA.Nephrol Dial Transplant. 2021; 36: 87-94Crossref PubMed Google Scholar Vaccinations are indispensable to protect this vulnerable population. Unfortunately, >50% of solid organ recipients do not mount antibody responses after 2 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines.2Sattler A. Schrezenmeier E. Weber U.A. et al.Impaired humoral and cellular immunity after SARS-CoV2 BNT162b2 (Tozinameran) prime-boost vaccination in kidney transplant recipients.J Clin Invest. 2021; 131e150175Crossref PubMed Scopus (192) Google Scholar,3Miele M. Busà R. Russelli G. et al.Impaired anti-SARS-CoV-2 humoral and cellular immune response induced by Pfizer-BioNTech BNT162b2 mRNA vaccine in solid organ transplanted patients.Am J Transplant. 2021; 21: 2919-2921Crossref PubMed Scopus (58) Google Scholar We hypothesized that a third vaccine dose elicits protective humoral and cellular immune response in primary nonresponders. Ten RTRs under immunosuppression (Supplementary Table S1) without measurable SARS-CoV-2 spike antibodies 4 weeks after a second dose of BNT162b2 (Pfizer–BioNTech) received a third vaccine dose (mRNA-1273; Moderna), which was well-tolerated. For a description of the employed methods, see the Supplementary Methods. The third vaccination induced seroconversion in 6 subjects (60%) with a median antibody titer concentration of 542 (interquartile range, 478–923) U/ml and neutralizing capacity (Figure 1a and b). Correspondingly, a strong increase in the magnitude of SARS-CoV-2 spike (S)-protein–reactive T-cell immunity (median, 0.08%) was observed in 9 subjects (90%; Figure 1c and d and Supplementary Table S1) with T-cell frequencies comparable to healthy individuals.2Sattler A. Schrezenmeier E. Weber U.A. et al.Impaired humoral and cellular immunity after SARS-CoV2 BNT162b2 (Tozinameran) prime-boost vaccination in kidney transplant recipients.J Clin Invest. 2021; 131e150175Crossref PubMed Scopus (192) Google Scholar Increased frequencies of cytokine-producing T cells and follicular T-helper cells indicated a gain of antiviral functionality (Figure 1e–i). Compared with recent data showing increased SARS-CoV-2 S-protein antibody levels in transplant patients after 3-dose SARS-CoV-2 mRNA vaccination,4Kamar N. Abravanel F. Marion O. et al.Three doses of an mRNA Covid-19 vaccine in solid-organ transplant recipients.N Engl J Med. 2021; 385: 661-662Crossref PubMed Scopus (632) Google Scholar,5Werbel W.A. Boyarsky B.J. Ou M.T. et al.Safety and immunogenicity of a third dose of SARS-CoV-2 vaccine in solid organ transplant recipients: a case series.Ann Intern Med. 2021; 174: 1330-1332Crossref PubMed Scopus (256) Google Scholar our study provides a deeper immunologic characterization of vaccination-specific immunity, as demonstrated by antibody neutralizing capacity and spike-reactive T-cell immunity. In summary, a third dose of an mRNA vaccine elicits a humoral and cellular response in 60% and 90% of RTR patients, respectively, who failed the primary vaccination. Although larger cohort studies with longer observation time are needed to confirm our results, the exceptionally high risk of fatal COVID-19 in RTRs supports consideration of a third vaccination in clinical practice. Data will be available on request. We feel deep gratitude to the patients who donated their blood samples and clinical data for this project. We would like to acknowledge the excellent technical assistance as well as the expertise of immune diagnostic laboratory (Sarah Skrzypczyk, Eva Kohut, Julia Kurek, and Jan Zapka) of the Center for Translational Medicine at Marien Hospital Herne. This work was supported by grants of the Mercator Foundation, German Federal Ministry of Education and Research (BMBF) NoChro (No. 13GW0338B), and AiF/ZIM project EpiCov. Download .pdf (.36 MB) Help with pdf files Supplementary File (PDF)