Cellular and Humoral Responses in Dialysis Patients after Vaccination with the BNT162b2 or mRNA-1273 Vaccines
Abstract
:Simple Summary
Abstract
1. Introduction
2. Vaccine-Elicited Humoral Immune Response among Dialysis Patients
2.1. Studies Assessing a Two-Dose mRNA-Based Vaccination Regimen on the Humoral Response in Dialysis Patients
2.2. Effect of a Third and/or Fourth Booster Vaccine Dose on the Humoral Response in Dialysis Patients
3. Vaccine-Elicited Cellular Immune Response among Dialysis Patients
3.1. Studies Assessing a Two-Dose mRNA-Based Vaccination Regimen on the Cellular Response in Dialysis Patients
3.2. Effect of a Third and/or Fourth booster Vaccine Dose on the Cellular Response in Dialysis Patients
4. Variables Affecting Immune Response in Dialysis Patients
5. Recommended Strategies to Augment the Immune Response to SARS-CoV-2 Vaccination in Dialysis Patients
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Author; Country | Study Design; Sample Size | Mean and/or Median Age (±SD) (yrs.) | Sex Males/Females | Vaccine Type; Number of Doses (Dosage Interval) | Timing of Blood Sampling Post Vaccination | Diagnostic Test; Criteria for Positive Response | Response Rate |
---|---|---|---|---|---|---|---|
Humoral: | |||||||
ARCHITECT IgG II | |||||||
Bertrand et al. [18]; France | Cohort; 45 KTRs, 10 HDPs | KTRs: 63.5 ± 16.3 HDPs: 71.2 ± 16.4 | KTRs: 23/22; HDPs: NR | BNT162b2; 2 (21 days) | 1 month | Quant test (Abbott); titers >50 AU/mL Cellular: Detection of SARS-CoV-2– reactive IFNγ-producing T-cells; SFC > 3 SDs of spot | KTRs:
|
numbers in wells | |||||||
without antigens | |||||||
Humoral: SARS- | |||||||
CoV-2 IgG kit | Convalescent HDPs: | ||||||
Blazquez-Navarro et al. [19]; Germany | Cohort; 18 Convalescent HDPs, 22 Vaccinated HDPs | Convalescent HDPs: 62 (39–78) Vaccinated HDPs: 67(43–80) | 24/16 | BNT162b2; 2 (NR) | Convalescent HDPs: median 60 days post vaccination (17–441); vaccinated HDPs: median 158 post infection (61–290) | (EUROIMMUN, Lübeck, Germany); NR Cellular: Cytokine expression by S-protein activated T |
|
cells (IFNγ, IL2, |
| ||||||
TNFα); NR | |||||||
Humoral: Siemens | |||||||
Healthineers Atellica | |||||||
IM SARS-CoV-2 IgG | |||||||
(sCOVG) assay; Anti- | |||||||
Broseta et al. [20]; Spain | Cohort; 175 HDPs | 70.90 ± 14.96 | 118/57 | 100 HDPs: mRNA- 1273; 2 (28 days) 75 HDPs: BNT162b2; 2 (21 days) | 3 weeks | S1-RBD IgG ≥ 1U/mL Cellular:Intracellular Cytokine Stimulation Assay; Flow cytometric detection > 10 events of CD4+ IFNγ+ CD69+, | Humoral: 95.4% Cellular: 62% |
with greater than 2-fold | |||||||
change compared with | |||||||
the unstimulated | |||||||
condition | |||||||
Humoral: Maglumi | |||||||
SARS-CoV-2 S-RBD | HDPs: -Humoral: 82% | ||||||
Espi et al. [21]; France | Case-Control; 106 HDPs, 30 Controls | HDPs: 64.9 ± 15.2 Controls: 46.6 ± 14.8 | HDPs: 69/37 Controls: 14/16 | BNT162b2; 2 (3–5 weeks) | 10–14 days | IgG test (Snibe Diagnostic); titers > 1 AU Cellular: QuantiFERON SARS- |
|
CoV-2 test (Qiagen); | (CD4+), 70% (CD8+) | ||||||
NR | |||||||
Humoral: anti-SARS- | DPs: -Humoral: 55.56% (1w), 88.9% (3w), 84.37% (10w)
| ||||||
CoV-2-S1 ELISA | |||||||
DPs: 74.0 (IQR | (EuroimmunMedizinisch | ||||||
Schrezenmeier et al. [22]; Germany | Case-Control; 36 DPs, 44 Controls | 66.0, 82.0) Controls: 80.0 (IQR 75.75, | DPs 25/11 Controls: 14/30 | BNT162b2; 2 (21 days) | ≈3–4 and ≈10 weeks | eLabordiagnostika AG, Lübeck, Germany); OD > 1.1 | |
82.25) | Cellular: interferon- | ||||||
gamma release assay | |||||||
(IGRA) | |||||||
Humoral: | |||||||
MULTICOV-AB; | DPs: -Humoral: 95% | ||||||
Strengert et al. [23]; Germany | Case-Control; 81 HDPs, 34 Controls | HDPs: 69 (±18) Controls: 54.5 (±15) | HDPs: 47/34 Controls: 6/28 | BNT162b2; 2 (21 days) | 21 days | NR Cellular: SARS-CoV-2 Interferon Gamma Release Assay; |
|
IFNγ concentrations |
| ||||||
>200 mIU/mL | |||||||
Humoral: SARS-CoV-2 | |||||||
specific IgG- or IgA- | |||||||
antibody reactions | |||||||
(S1,NCP,RBD) | |||||||
(Euroimmun); de novo | |||||||
antibody development | |||||||
Cellular: SARS-CoV- | |||||||
2 specific IFNγ | |||||||
Stumpf et al. [24]; Germany | Case-Control; 1256 DPs, 368 KTRs, 144 Controls | DPs: 67.6 ± 14; KTRs: 57.3 ± 13.7 Controls: 48 ± 11.9 | DPs: 818/438; KTRs: 241/127 Controls: 34/110 | 1412: mRNA-1273;2 (28 days) 356: BNT162b2; 2 (21 days) | 4–5 weeks | release assay (IGRA); results ≥ 100 mIU/mL and deep immunophenotyping by FACS analysis; CD4+ T-cells expressing CD154 | HDPs: -seropositive: 91.8%
|
and CD137 and | |||||||
CD8+ T-cells | |||||||
expressing CD137 | |||||||
with simultaneous | |||||||
production of at least | |||||||
one of | |||||||
IL2/IL4/IFNγ/TNFα/ | |||||||
GrzB | |||||||
Anti-SARS-CoV-2 | HDPs: seropositive: 91.8% KTRs: seropositive 19.6% Antibody titers: HDPs > KTRs (5759.9 ± 6771 vs. 113.9 ± 300 g/dL) | ||||||
Antibody Response: | |||||||
-Serologic response was | |||||||
Duni et al. [25]; Greece | Case Control; 34 HDPs, 54 KTR | HD:69.4; KTRs: 58.2 | HD:23/11; KTRs: 38/54 | BNT162b2; 2 (21 days) | 21 days | assessed by using the ARCHITECT IgG II Quant test (Abbott) | |
-Flow Cytometry | |||||||
Analysis |
Author; Country | Study Design; Sample Size | Mean and/or Median Age (±SD) (yrs.) | Sex Males/Females | Vaccine Type; Number of Doses (Dosage Interval) | Timing of Blood Sampling Post Vaccination | Diagnostic Test; Criteria for Positive Response | Response Rate |
---|---|---|---|---|---|---|---|
Verdier et al. [26]; France | Retrospective observational; 142 HDPs | 71.1/74.0 | 103/39 | BNT162b2; 3 (21 days between doses 1 and 2, not clearly stated between doses 2 and 3) | Sample 1: 46 days after second dose Sample 2: 35 days after third dose | Humoral: Siemens Atellica IM anti-S1-RBD SARS-CoV-2 IgG assay (Siemens Healthcare GmbH, Erlangen, Germany); titers > 1.2 U/mL | Humoral: 82.9% after two doses, 95.8% after three doses |
Agur et al. [27]; Israel | Prospective comparative; 80 HDPs 56 controls | HDPs: 72.61 ± 11.78 Controls: 69.3 ± 5.32 | HDPs: 56/24 Controls: 27/27 | BNT162b2; 3 (21 days between doses 1 and 2, at least 6 months between doses 2 and 3) | Sample 1: 21 days before third dose Sample 2: 21 days after third dose | Humoral: anti-S1-RBD SARS-CoV-2 IgG II Quant assay (Abbott); titers >50 AU/mL | Humoral: 78% after two doses, 96% after three doses |
Becker et al. [28].; Germany | Prospective comparative; 50 HDPs 33 controls | HDPs: 69.5 (60–79) Controls: 42 (32–55) | HDPs: 31/19 Controls: 10/23 | BNT162b; 3 (21 days between doses 1 and 2, 6 months between doses 2 and 3) mRNA-1273; 1 (4 months between doses 3 and 4) | Samples 1 and 2: 3 and 16 weeks after second dose Samples 3 and 4: 4 and 17 weeks after third dose Sample 5: 3 weeks after fourth dose | Humoral: MULTICOV-AB and RBDCoV-ACE2 assays (cut-offs not stated) Cellular: SARS-CoV-2 IFNγ Release Assay and IFNγ ELISA (Euroimmun); titers > 200 mIU/mL | Humoral: varied according to antibody measured and variant of concern studied, but incremental antibody response with each vaccine dose. Humoral: incremental cellular response after the third and fourth vaccine doses. |
Gallego-Valcarce et al. [29]; Spain | Prospective observational; 178 HDPs | 68.7 ± 14.5 | 113/65 | 40 HDPs: BNT162b2; 3 138 HDPs: mRNA- 1273; 3 (4 weeks between doses 1 and 2, 5 months between doses 2 and 3) | Every month starting from the first dose, and up to 4 months after the third dose | Humoral: anti-SARS-CoV-2 S1- RBD IgG assay (Abbott Laboratories, Chicago, Illinois); titers > 50 AU/mL | Humoral: 77.8% after two doses, 97% after three doses |
Humoral: anti- | |||||||
Melin et al. [30]; Sweden | Retrospective observational; 50 HDPs | 69.4 ± 14.1 | 31/19 | BNT162b2; 3 (4 weeks between doses 1 and 2, 6–8 months between doses 2 and 3) | Samples 1 and 2: 7–15 weeks and 6–8 months after dose 2 Samples 3 and 4: 3 weeks and 3 months after dose 3 | SARS-CoV-2 S1- RBD IgG II Quant assay; titers >100 AU/mL and anti-SARS-CoV-2 anti-N IgG assay; titers > 1.4 S/COCellular: IFNγ level measurement | Humoral: 88% after two doses, 95% after three doses Cellular: 55% after two doses, 85% and 71% 3 weeks and 3 months after three doses, respectively |
(ELISPOT) | |||||||
Broseta et al. [31]; Spain | Prospective observational; 153 HDPs | 72.12 ± 14.44 | 84/69 | 71 HDPs: BNT162b2; 3 82 HDPS: mRNA- 1273; 3 (dosage intervals not specified) | Two weeks after the third dose | Humoral: Siemens Healthineers Atellica IM SARS-CoV-2 IgG (sCOVG) assay; 1–150 U/mL: non- or weak responder, >150 U/mL: responder | Humoral: 97.4% seroconverted (> 1 U/mL) after the third dose (qualitative outcome only) |
Quiroga et al. [32]; Spain | Prospective observational; 164 PDPs | 62 ± 13 | 113/56 | 123 PDPs: mRNA- 1273; 3 or 4 (intervals not specified) 41 PDPs: BNT162b2; 3 or 4 (intervals not specified) | 28 days, 3 months, and 6 months after two doses, 6 and 12 months after three doses, 12 months after four doses | Humoral: CLIA, COVID-19 Spike Quantitative Virclia IgG Monotest (Vircell SL, Grenada, Spain); titers > 36 IU/mL | Humoral: 80% 6 months after 2 doses, 97% 12 months after 3 doses, 100% 12 months after 4 doses (not statistically significant to 3-dose schedule) |
Humoral: Elecsys anti- | Humoral: 90% seroconversion after 2 doses (50% after adjustment for anti-SARS-CoV-2-S-Ab levels using surrogate neutralization test), 100% after 3 doses. 97.3% HDPs with adequate neutralizing Abs after three doses | ||||||
SARS-CoV-2-Nc-Abs and | |||||||
anti-SARS-CoV-2-S-Ab | |||||||
(Roche Diagnostics, | |||||||
Kohmer et al. [33]; Germany | Prospective observational; 194 DPs (167 HDPs, 27 PDPs) | DPs: 69.6 ± 14.2 (HDPs: 71.0 ± 13.9, PDPs: 61.6 ± 13.8) | DPs: 110/84 (HDPs: 93/74, PDPs: 17/10) | BNT162b2; 2 (intervals not specified) mRNA-1273; 1 (6 months after second dose) | 4 and 10–12 weeks after two doses, 4 weeks after third dose | Mannheim, Germany); titers > 0.8 U/mL. Measurement of SARS-CoV-2-NT-Abs with the ELISA-based GenScript SARS-CoV-2 Surrogate | |
Virus Neutralization Test | |||||||
Kit (GenScript Biotech, NJ, | |||||||
USA); inhibition > 30% | |||||||
was considered positive |
Recommended Strategy | Comments/Notable Considerations |
---|---|
Reinforce importance of vaccination in dialysis patients, ensure vaccine availability in dialysis patients, promote patient–physician relationships to establish goals and promote the benefits of vaccination | Although not directly associated with augmentation of the immune response, these measures are deemed crucial to increase vaccination rates in dialysis patients. |
Primary vaccination series with an mRNA-based vaccine (either mRNA-1273 or BNT162b2) | Most studies report greater immune response outcomes with an mRNA-based vaccine when compared to other vaccine types in dialysis patients. Although the mRNA-1273 has been shown to confer higher antibody titers in dialysis patients compared to the BNT162b2 vaccine, more studies are needed to assess whether recommendations about a specific mRNA-based vaccine are justified. Currently, either vaccine can be recommended, and factors such as local availability as well as potential adverse effects from a specific vaccine need to be taken into account. |
Booster dose administration with an mRNA-based vaccine | Booster doses significantly accentuate the immune response to vaccination in dialysis patients. Most studies have assessed an mRNA-based booster dose regimen. The dosing interval between the booster dose and last dose of primary vaccine series, intervals between booster doses, and the number of booster doses administered are factors that need to be assessed in future studies. |
Periodic laboratory monitoring of the humoral and cellular responses to vaccination in dialysis patients | Although not directly associated with augmentation of the immune response following vaccination, monitoring of antibody titers, antibody neutralization capacity, and cellular response after vaccination can identify patients at risk that require additional booster doses due to the inevitable waning of immunity that ensues following vaccination, especially in dialysis patients. |
Aggressive control of risk factors that negatively impact vaccine efficacy | It is crucial to eliminate or at least minimize the impact of well-reported risk factors that negatively correlate with immune responses after vaccination. Some variables, however, such as the use of an immunosuppressive regimen in kidney transplant patients, are hard to address, and, in such cases, careful monitoring and management of other risk factors may prove beneficial. |
Inclusion of dialysis patients in trials exploring vaccine efficacy and safety | Studies that contemplate vaccine outcomes and safety in dialysis patients are needed to learn more about the immune response alterations in this population with regards to SARS-CoV-2 vaccination. This could solidify an appropriate vaccine strategy that is safe and effective. |
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Mavrovouniotis, I.; Fylaktou, A.; Stagou, M.; Ouranos, K.; Lioulios, G.; Evgenikaki, E.; Exindari, M.; Gioula, G. Cellular and Humoral Responses in Dialysis Patients after Vaccination with the BNT162b2 or mRNA-1273 Vaccines. Life 2023, 13, 474. https://doi.org/10.3390/life13020474
Mavrovouniotis I, Fylaktou A, Stagou M, Ouranos K, Lioulios G, Evgenikaki E, Exindari M, Gioula G. Cellular and Humoral Responses in Dialysis Patients after Vaccination with the BNT162b2 or mRNA-1273 Vaccines. Life. 2023; 13(2):474. https://doi.org/10.3390/life13020474
Chicago/Turabian StyleMavrovouniotis, Ilias, Asimina Fylaktou, Maria Stagou, Konstantinos Ouranos, Georgios Lioulios, Efthimia Evgenikaki, Maria Exindari, and Georgia Gioula. 2023. "Cellular and Humoral Responses in Dialysis Patients after Vaccination with the BNT162b2 or mRNA-1273 Vaccines" Life 13, no. 2: 474. https://doi.org/10.3390/life13020474