A third dose SARS‑CoV‑2 BNT162b2 mRNA vaccine results in improved immune response in hemodialysis patients

Keywords: Hemodialysis, chronic kidney disease, humoral and cellular immune response, SARS-CoV-2 BNT162b2 mRNA vaccine


Background: The hemodialysis (HD) population has been a vulnerable group during the coronavirus disease 2019 (COVID-19) pandemic. Advanced chronic kidney disease with uremia is associated with weaker immune response to infections and an attenuated response to vaccines. The aim of this study was to study the humoral and cellular response to the second and third doses of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‑CoV‑2) BNT162b2 mRNA vaccine in HD patients and to follow the response over time.

Methods: The patients received their first two vaccine doses from 28 December 2020 within a 4-week interval and the third dose in September 2021 and were followed-up for humoral and cellular immune response at 1) 7–15 weeks and 2) 6–8 months after dose two (no t-cell reactivity measured), and 3) 3 weeks and 4) 3 months after dose three. Fifty patients were initially enrolled, and 40 patients were followed during the entire study. Levels of COVID-19 (SARS-CoV-2) IgG antibody against the Spike antigen (anti-S) and T-cell reactivity testing against the Spike protein using Enzyme-Linked ImmunoSpot (ELISPOT) technology were evaluated.

Results: IgG antibodies to anti-S were detected in 35 (88%) of the 40 patients 7–15 weeks after vaccine dose two, 31 (78%) were positive, and 4 (10%) borderline. The median anti-S titer was 606 Abbott Units/milliliter (AU/mL) (interquartile range [IQR] 134–1,712). Three months after the third dose, anti-S was detected in 38 (95%) of 40 patients (P < 0.01 compared to after dose two), and the median anti-S titer was 9,910 AU/mL (IQR 2,325–26,975). Cellular reactivity was detected in 22 (55%), 34 (85%), and 28 (71%) of the 40 patients, and the median T-cell response was 9.5 (IQR 3.5–80), 51.5 (14.8–132), and 19.5 (8.8–54.2) units, respectively, for 6–8 months after dose two, 3 weeks, and 3 months after dose three.

Conclusions: Our data show that a third dose of SARS‑CoV‑2 BNT162b2 mRNA vaccine gives a robust and improved immunological response in HD patients, but a few patients did not develop any anti-S response during the entire study, indicating the importance to monitor the vaccine response since those who do not respond could now be given monoclonal antibodies if they contract a COVID-19 infection or in the future antivirals.


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1. Segelmark M, Segelmark L, Smolander S, Rydell H, Evans M, Stendal M. COVID-19 related mortality in Swedish patients with renal replacement therapy. Läkartidningen 2021;118:21051.

2. Savino M, Santhakumaran S, Evans KM, Steenkam R, Benoy-Deeney F, Medcalf JF, Nitsch D. Outcomes of patients with COVID-19 on kidney replacement therapy: a comparison among modalities in England. Clin Kidney J 2021;14:2573–81. doi: 10.1093/ckj/sfab160

3. Betjes MGH. Uremia-associated immunological aging and severity of COVID-19 infection. Front Med 2021;8:675573. doi: 10.3389/fmed.2021.675573

4. Kato S, Chmielewski M, Honda H, Pecoits-Filho R, Matsuo S, Yuzawa Y, Tranaeus A, Stenvinkel P, Lindholm B. Aspects of immune dysfunction in end-stage renal disease. Clin J Am Soc Nephrol 2008;3:1526–33. doi: 10.2215/CJN.00950208

5. Ishigami J, Matsushita K. Clinical epidemiology of infectious disease among patients with chronic kidney disease. Clin Exp Nephrol 2019;23:437–47. doi: 10.1007/s10157-018-1641-8

6. Ben-Dov IZ, Tzukert K, Aharon M, Pri-Chen H, Oster Y, Oiknine-Djian E, Wolf DG, Dranitzki Elhalel M. Response to tozinameran (BNT162b2) booster in twice-vaccinated kidney transplant and maintenance dialysis patients. J Nephrol 2022;35:761–3. doi: 10.1007/s40620-021-01235-3

7. Melin J, Svensson MK, Albinsson B, Winqvist O, Pauksens K. Humoral and cellular response to SARS-CoV-2 BNT162b2 mRNA vaccine in hemodialysis patients. BMC Immunol 2021;22:70. doi: 10.1186/s12865-021-00458-0

8. Yen JS, Wang IK, Yen TH. COVID-19 vaccination & dialysis patients: why the variable response. QJM Int J Med 2021;114:440–4. doi: 10.1093/qjmed/hcab171

9. Goldberg Y, Mandel M, Bar-On YM, Bodenheimer O, Freedman L, Haas EJ, Milo R, Alroy-Preis S, Ash N, Huppert A. Waning immunity after the BNT162b2 vaccine in Israel. N Engl J Med 2021;385:e85. doi: 10.1056/NEJMoa2114228

10. Berar-Yanay N, Freiman S, Shapira M, Saffoury A, Elemy A, Hamze M, Elhaj M, Zaher M, Matanis L, Anis Armaly Z. Waning humoral response 3 to 6 months after vaccination with the SARS-COV-2 BNT162b2 mRNA vaccine in dialysis patients. J Clin Med 2021;11:64. doi: 10.3390/jcm11010064

11. Barda N, Dagan N, Cohen C, Hernán MA, Lipsitch M, Kohane IS, Reis† BY, Balicer RD. Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study. Lancet 2021;398:2093–100. doi: 10.1016/S0140-6736(21)02249-2

12. Pérez-Then E, Lucas C, Silva Monteiro V, Miric M, Brache V, Cochon L, Vogels CBF, Malik AA, De la Cruz F, Jorge A, De los Santos M, Leon P, Breban MI, Billig K, Yildirim I, Pearson C, Downing R, Gagnon E, Muyombwe A, Razeq J, Campbell M, Ko AI, Omer SB, Grubaugh ND, Vermund SH, Iwasaki A. Neutralizing antibodies against the SARS-CoV-2 delta and omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination. Nat Med 2022;28:481–5. ​doi: 10.1038/s41591-022-01705-6

13. Wu M, Wall EC, Carr EJ, Harvey R, Townsley H, Mears HV, Adams L, Kjaer S, Kelly G, Warchal S, Sawyer C, Kavanagh C, Queval CJ , Ngai Y, Hatipoglu E, Ambrose K, Hindmarsh S, Beale R, Gamblin S, Howell M, Kassiotis G, Libri V, Williams B, Gandhi S, Swanton C, Bauer DLV. Three-dose vaccination elicits neutralising antibodies against omicron. Lancet 2022;399:715–17. doi: 10.1016/S0140-6736(22)00092-7

14. Cheng SMS, Ka Pun Mok C, Leung YWY, Ng SS, Chan KCK, Ko FW, Chen C, Yiu K, Lam BHS, Lau EHY, Chan KKP, Luk LLH, Li JKC, Tsang LCH, Poon LIM, Hui DSC, Peiris M. Neutralizing antibodies against the SARS-CoV-2 omicron variant following homologous and heterologous CoronaVac or BNT162b2 vaccination. Nat Med 2022;28:486–9. doi: 10.1038/s41591-022-01704-7

15. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Methodol 1995;57:289–300. doi: 10.1111/j.2517-6161.1995.tb02031.x

16. Yekutieli D, Benjamini Y. Resampling-based false discovery rate controlling multiple test procedures for correlated test statistics. J Stat Plan Inference 1999;82:171–96. doi: 10.1016/S0378-3758(99)00041-5

17. Kumar BV, Connors TJ, Farber DL. Human T cell development, localization, and function throughout life. Immunity 2018;48:202–13. doi: 10.1016/j.immuni.2018.01.007
How to Cite
Melin J., Svensson M. K., Albinsson B., Winqvist O., & Pauksens K. (2022). A third dose SARS‑CoV‑2 BNT162b2 mRNA vaccine results in improved immune response in hemodialysis patients. Upsala Journal of Medical Sciences, 127(1). https://doi.org/10.48101/ujms.v127.8959
Original Articles