Diminishing Immune Responses against Variants of Concern in Dialysis Patients 4 Months after SARS-CoV-2 mRNA Vaccination

Dulovic, Alex; Strengert, Monika; Ramos, Gema Morillas; Becker, Matthias; Griesbaum, Johanna; Junker, Daniel; Lürken, Karsten; Beigel, Andrea; Wrenger, Eike; Lonnemann, Gerhard; Cossmann, Anne; Stankov, Metodi V.; Dopfer-Jablonka, Alexandra; Kaiser, Philipp; Traenkle, Bjoern; Rothbauer, Ulrich; Krause, Gérard; Schneiderhan‐Marra, Nicole; Behrens, Georg M. N.

doi:10.3201/eid2804.211907

Cited by 21 publications

(20 citation statements)

References 24 publications

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“…Detailed information on the study populations can be found in Table 1, S1 and S2. Consistent with our previous reports (16, 17), IgG responses towards the original B.1 isolate in vaccinated dialysis patients were significantly reduced (p=4·68*10 −5 , Mann-Whitney-U test) when compared to the control group and declined after the second vaccination to comparable levels in both groups (p=7·33*10 −2 , Mann-Whitney-U test, Fig. 2a).…”

Section: Resultssupporting

confidence: 91%

“…(16) and Dulovic et al . (17). (b) T-cell responses assessed by IGRA and B-cell responses assessed by ACE2-RBD competition assay towards the RBD of B.1, Delta, Omicron BA.1 isolates were plotted for correlation analysis (b).…”

Section: Resultsmentioning

confidence: 99%

“…This is a follow-up study in haemodialysis patients and control individuals, for which the results for haemodialysis patients after a complete two-dose BNT162b2 vaccination (16) and subsequent decline (17) have been previously reported. Blood samples were taken before start of dialysis (n=50) or from healthcare workers (n=33), who participated in the COVID-19 contact (CoCo) study served (18) as non-dialysed control population.…”

Section: Methodsmentioning

confidence: 95%

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Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients

Becker

Cossmann

Luerken

et al. 2022

Preprint

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Background Haemodialysis patients are at-risk for severe COVID-19 and were among the first to receive a fourth COVID-19 vaccination. Methods We analysed humoral responses by multiplex-based IgG measurements against the receptor-binding domain (RBD) and ACE2-binding inhibition towards variants of concern including Omicron in haemodialysis patients and controls after triple BNT162b2 vaccination and in dialysis patients after a fourth full-dose of mRNA-1273. T-cell responses were assessed by interferon gamma release assay. Findings After triple BNT162b2 vaccination, anti-RBD B.1 IgG and ACE2 binding inhibition reached peak levels in dialysis patients, but remained inferior compared to controls. Whilst we detected B.1-specific ACE2 binding inhibition in 84% of dialysis patients after three BNT162b2 doses, binding inhibition towards the Omicron variant was only 38% and declining to 16% before the fourth vaccination. By using mRNA-1273 as fourth dose, humoral immunity against all SARS-CoV-2 variants tested was strongly augmented with 80% of dialysis patients having Omicron-specific ACE2 binding inhibition. Modest declines in T-cell responses in dialysis patients and controls after the second vaccination were restored by the third BNT162b2 dose and significantly increased by the fourth vaccination. Conclusions A fourth full-dose mRNA-1273 after triple BNT162b2 vaccination in haemodialysis patients leads to efficient humoral responses against Omicron. Our data support current national recommendation and suggest that other immune-impaired individuals may benefit from this mixed mRNA vaccination regimen. Funding Initiative and Networking Fund of the Helmholtz Association of German Research Centres, EU Horizon 2020 research and innovation program, State Ministry of Baden-Wuerttemberg for Economic Affairs, Labour and Tourism, European Regional Development Fund

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 95%

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Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients

Becker

Cossmann

Luerken

et al. 2022

Preprint

Self Cite

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“…BNT162b2 vaccine-induced antibodies decline rapidly in the general population as well as in dialysis patients [4,6]. The emergence of new COVID-19 variants along with the waning of the protective antibody titer [3,4,18] raised the need for a booster dose of the vaccine [20,22].…”

Section: Discussionmentioning

confidence: 99%

“…In January 2022, during the B.1.1.529 (Omicron) variant wave and waning immunity [18], a second booster dose (fourth vaccine dose) was also approved by the Israeli authorities and later by the FDA and CDC. The immunogenic effect of the BNT162b2 vaccine second booster in dialysis patients is still unclear [19,20].…”

Section: Introductionmentioning

confidence: 99%

BNT162b2 Booster Vaccination Induced Immunity against SARS-CoV-2 Variants among Hemodialysis Patients

et al. 2022

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Background: The emergence of new SARS-CoV-2 variants, which evade immunity, has raised the urgent need for multiple vaccine booster doses for vulnerable populations. In this study, we aimed to estimate the BNT162b2 booster effectiveness against the spread of coronavirus variants in a hemodialysis population. Methods: We compared humoral and cell-mediated immunity in 100 dialysis patients and 66 age-matched volunteers, before and 2–3 weeks following the first booster vaccine dose. Participants were assessed for anti-spike (RBD) antibody titer, neutralizing antibodies against B.1.617.2 (Delta) and B.1.1.529 (Omicron) variants, spike-specific T-cell responses by FACS and infection outbreak after the first and second booster. Results: Anti-spike antibody titer was significantly increased following the booster, with reduced humoral and cellular response in the dialysis patients. Neutralizing antibody levels increased significantly after the booster dose, with an inferior effect (≤2 fold) against Omicron compared with the Delta variant. Furthermore, CD4+ and CD8+ T-cell activation by Delta spike protein was preserved in 70% of PBMCs from the dialysis patients. A second booster dose tended to reduce breakthrough infections in the dialysis patients. Conclusions: Until the release of an updated vaccine, BNT162b2 booster doses will improve the humoral and cell-mediated immunity against variants. These findings support the importance of repetitive booster doses for hemodialysis patients.

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Immunogenicity of COVID‐19 mRNA vaccines in hemodialysis patients: Systematic review and meta‐analysis

Falahi

Sayyadi

Kenarkoohi

2022

Health Science Reports

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Background and Aims Vaccine response is a concern in hemodialysis patients. Given that hemodialysis patients were not included in clinical trials, we aimed to synthesize the available evidence on the immunogenicity of coronavirus disease 2019 (COVID‐19) mRNA vaccines in hemodialysis patients. Methods We searched Scopus, PubMed, Sciencedirect, and finally google scholar databases for studies on COVID‐19 mRNA‐vaccines immunogenicity in hemodialysis patients up to December 1, 2021. Eligible articles measured antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike or Receptor‐Binding Domain Antibody (S/RBD) postimmunization with COVID‐19 mRNA vaccines. The immunogenicity of the vaccine was evaluated using seroconversion rates measured between 21 and 30 days after the first immunization and between 14 and 36 days post the second dose. We included studies including participants without a history of COVID‐19 before vaccination. Healthy controls or health‐care workers served as the control groups. After selecting eligible articles, the data were finally extracted from included articles. We used a random effects model to estimate the pooled seroconversion rate after COVID‐19 mRNA vaccine administration. We assessed the heterogeneity between studies with the I 2 statistical index. Result We selected 39 eligible citations comprising 806 cases and 336 controls for the first dose and 6314 cases and 927 controls for the second dose for statistical analysis. After the first dose of mRNA vaccines, the seroconversion rate was 36% (95% confidence interval [CI]: 0.24–0.47) and 68% (95% CI: 0.45–0.91) in hemodialysis patients and the control group, respectively. While seroconversion rate after the second dose of mRNA vaccines was 86% (95% CI: 0.81–0.91) and 100% (95% CI: 1.00–1.00) in hemodialysis patients and the control group, respectively. Conclusion Although the immune response of hemodialysis patients to the second dose of the SARS‐CoV‐2 mRNA vaccine is very promising, the seroconversion rate of dialysis patients is lower than healthy controls. Periodically assessment of antibody levels of hemodialysis patients at short intervals is recommended.

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Diminishing Immune Responses against Variants of Concern in Dialysis Patients 4 Months after SARS-CoV-2 mRNA Vaccination

Cited by 21 publications

References 24 publications

Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients

Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients

BNT162b2 Booster Vaccination Induced Immunity against SARS-CoV-2 Variants among Hemodialysis Patients

Immunogenicity of COVID‐19 mRNA vaccines in hemodialysis patients: Systematic review and meta‐analysis

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