Improved SARS-CoV-2 neutralization of Delta and Omicron variants of concern after fourth vaccination in hemodialysis patients

Cheng, Cho-Chin; Platen, Louise; Christa, Catharina; Tellenbach, Myriam; Kappler, Verena; Bester, Romina; Liao, Bo-Hung; Holzmannn-Littig, Christopher; Werz, Maia Lucia; Schoenhals, Emely; Platen, Eva; Eggerer, Peter; Treguer, Laetitia; Kuechle, Claudius; Schmaderer, Christoph; Heemann, Uwe; Renders, Lutz; Protzer, Ulrike; Braunisch, Matthias C.

doi:10.1101/2022.06.22.22276787

Cited by 3 publications

(6 citation statements)

References 24 publications

(36 reference statements)

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“…Our study is, to our knowledge, the only study examining the longitudinal humoral and cellular immune response towards the most recent SARS-CoV-2 isolates in haemodiaylsis patients after administration of consistent vaccination regimens starting with a triple dose of BNT162b2 followed by a fourth full-dose of mRNA-1273. Whilst other studies principally support the beneficial impact of a fourth vaccination dose on both antibody titers and neutralising potency towards SARS-CoV-2 B.1 and VoC isolates, often various vaccination regimens including heterologous vector-based/mRNA regimens were pooled in cohorts (14) or vaccine dosages not provided (13).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies reported improved SARS-CoV-2 humoral and cellular responses not only towards the original SARS-CoV-2 B.1 isolate but also Delta and Omicron VoC after a fourth vaccination in haemodialysis patients receiving either mRNA vaccines or vector-based formulations in combination with mRNA vaccines (13)(14)(15). However, targeted data on the most efficient dosing and vaccination scheme or even predictors of vaccination success in haemodialysis patients at-risk of severe COVID-19 and its associated mortality is limited.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Becker

Cossmann²,

Lürken³

et al. 2022

Front. Immunol.

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Haemodialysis patients respond poorly to vaccination and continue to be at-risk for severe COVID-19. Therefore, dialysis patients were among the first for which a fourth COVID-19 vaccination was recommended. However, targeted information on how to best maintain immune protection after SARS-CoV-2 vaccinations in at-risk groups for severe COVID-19 remains limited. We provide, to the best of our knowledge, for the first time longitudinal vaccination response data in dialysis patients and controls after a triple BNT162b2 vaccination and in the latter after a subsequent fourth full-dose of mRNA-1273. We analysed systemic and mucosal humoral IgG responses against the receptor-binding domain (RBD) and ACE2-binding inhibition towards variants of concern including Omicron and Delta with multiplex-based immunoassays. In addition, we assessed Spike S1-specific T-cell responses by interferon γ release assay. 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 detectable in 38% of samples 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. Our data support current advice for a four-dose COVID-19 immunisation scheme for at-risk individuals such as haemodialysis patients. We conclude that administration of a fourth full-dose of mRNA-1273 as part of a mixed mRNA vaccination scheme to boost immunity and to prevent severe COVID-19 could also be beneficial in other immune impaired individuals. Additionally, strategic application of such mixed vaccine regimens may be an immediate response against SARS-CoV-2 variants with increased immune evasion potential.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Becker

Cossmann²,

Lürken³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Our study is, to our knowledge, the only study examining the longitudinal humoral and cellular immune response towards the most recent SARS-CoV-2 isolates in haemodiaylsis patients after administration of consistent vaccination regimens starting with a triple dose of BNT162b2 followed by a fourth fulldose of mRNA-1273. Whilst other studies principally support the beneficial impact of a fourth vaccination dose on both antibody titers and neutralizing potency towards SARS-CoV-2 B.1 and VoC isolates, often various vaccination regimens including heterologous vector-based/mRNA regimens were pooled in cohorts (14) or vaccine dosages not provided (13) .…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies reported an improved SARS-CoV-2 humoral and cellular responses not only towards the original SARS-CoV-2 B.1 isolate but also Delta and Omicron VoC after a fourth vaccination in haemodialysis patients receiving either mRNA vaccines or vector-based formulations in combination with mRNA vaccines (13)(14)(15). However, targeted data on the most efficient dosing and vaccination scheme or even predictors of vaccination success in haemodialysis patients at-risk of severe COVID-19 and its associated mortality is limited.…”

Section: Introductionmentioning

confidence: 99%

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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“…The study adheres to the Declaration of Helsinki. It was approved by the Medical Ethics Committee of the Klinikum Rechts der Isar of the Technical University of Munich (approval number 163/21 S-SR, 19th March 2021) and registered at the Paul Ehrlich Institute (NIS592) (25).…”

Section: Methodsmentioning

confidence: 99%

Comparable cellular and humoral immunity upon homologous and heterologous COVID-19 vaccination regimens in kidney transplant recipients

et al. 2023

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BackgroundKidney transplant recipients (KTRs) are at high risk for a severe course of coronavirus disease 2019 (COVID-19); thus, effective vaccination is critical. However, the achievement of protective immunogenicity is hampered by immunosuppressive therapies. We assessed cellular and humoral immunity and breakthrough infection rates in KTRs vaccinated with homologous and heterologous COVID-19 vaccination regimens.MethodWe performed a comparative in-depth analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific T-cell responses using multiplex Fluorospot assays and SARS-CoV-2-specific neutralizing antibodies (NAbs) between three-times homologously (n = 18) and heterologously (n = 8) vaccinated KTRs.ResultsWe detected SARS-CoV-2-reactive T cells in 100% of KTRs upon third vaccination, with comparable frequencies, T-cell expression profiles, and relative interferon γ and interleukin 2 production per single cell between homologously and heterologously vaccinated KTRs. SARS-CoV-2-specific NAb positivity rates were significantly higher in heterologously (87.5%) compared to homologously vaccinated (50.0%) KTRs (P < 0.0001), whereas the magnitudes of NAb titers were comparable between both subcohorts after third vaccination. SARS-CoV-2 breakthrough infections occurred in equal numbers in homologously (38.9%) and heterologously (37.5%) vaccinated KTRs with mild-to-moderate courses of COVID-19.ConclusionOur data support a more comprehensive assessment of not only humoral but also cellular SARS-CoV-2-specific immunity in KTRs to provide an in-depth understanding about the COVID-19 vaccine–induced immune response in a transplant setting.

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Improved SARS-CoV-2 neutralization of Delta and Omicron variants of concern after fourth vaccination in hemodialysis patients

Cited by 3 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

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

Comparable cellular and humoral immunity upon homologous and heterologous COVID-19 vaccination regimens in kidney transplant recipients

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