Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients
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 vac...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-10-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1004045/full |
| _version_ | 1811229120871268352 |
|---|---|
| author | Matthias Becker Anne Cossmann Karsten Lürken Daniel Junker Jens Gruber Jennifer Juengling Gema Morillas Ramos Andrea Beigel Eike Wrenger Gerhard Lonnemann Metodi V. Stankov Alexandra Dopfer-Jablonka Alexandra Dopfer-Jablonka Philipp D. Kaiser Bjoern Traenkle Ulrich Rothbauer Ulrich Rothbauer Gérard Krause Gérard Krause Gérard Krause Nicole Schneiderhan-Marra Monika Strengert Monika Strengert Alex Dulovic Georg M. N. Behrens Georg M. N. Behrens Georg M. N. Behrens |
| author_facet | Matthias Becker Anne Cossmann Karsten Lürken Daniel Junker Jens Gruber Jennifer Juengling Gema Morillas Ramos Andrea Beigel Eike Wrenger Gerhard Lonnemann Metodi V. Stankov Alexandra Dopfer-Jablonka Alexandra Dopfer-Jablonka Philipp D. Kaiser Bjoern Traenkle Ulrich Rothbauer Ulrich Rothbauer Gérard Krause Gérard Krause Gérard Krause Nicole Schneiderhan-Marra Monika Strengert Monika Strengert Alex Dulovic Georg M. N. Behrens Georg M. N. Behrens Georg M. N. Behrens |
| author_sort | Matthias Becker |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T10:09:14Z |
| format | Article |
| id | doaj.art-c3c8a3ec127e47309ad52458e675fb17 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T10:09:14Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c3c8a3ec127e47309ad52458e675fb172022-12-22T03:37:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.10040451004045Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patientsMatthias Becker0Anne Cossmann1Karsten Lürken2Daniel Junker3Jens Gruber4Jennifer Juengling5Gema Morillas Ramos6Andrea Beigel7Eike Wrenger8Gerhard Lonnemann9Metodi V. Stankov10Alexandra Dopfer-Jablonka11Alexandra Dopfer-Jablonka12Philipp D. Kaiser13Bjoern Traenkle14Ulrich Rothbauer15Ulrich Rothbauer16Gérard Krause17Gérard Krause18Gérard Krause19Nicole Schneiderhan-Marra20Monika Strengert21Monika Strengert22Alex Dulovic23Georg M. N. Behrens24Georg M. N. Behrens25Georg M. N. Behrens26NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, GermanyDepartment for Rheumatology and Immunology, Hannover Medical School, Hannover, GermanyDepartment of Internal Medicine and Nephrology, Dialysis Centre Eickenhof, Langenhagen, GermanyNMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, GermanyNMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, GermanyNMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, GermanyDepartment for Rheumatology and Immunology, Hannover Medical School, Hannover, GermanyDepartment of Internal Medicine and Nephrology, Dialysis Centre Eickenhof, Langenhagen, GermanyDepartment of Internal Medicine and Nephrology, Dialysis Centre Eickenhof, Langenhagen, GermanyDepartment of Internal Medicine and Nephrology, Dialysis Centre Eickenhof, Langenhagen, GermanyDepartment for Rheumatology and Immunology, Hannover Medical School, Hannover, GermanyDepartment for Rheumatology and Immunology, Hannover Medical School, Hannover, GermanyGerman Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Hannover, GermanyNMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, GermanyNMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, GermanyNMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, GermanyPharmaceutical Biotechnology, University of Tübingen, Tübingen, GermanyGerman Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Hannover, GermanyDepartment Epidemiology, Helmholtz Centre for Infection Research, Braunschweig, GermanyTWINCORE GmbH, Centre for Experimental and Clinical Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, GermanyNMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, GermanyDepartment Epidemiology, Helmholtz Centre for Infection Research, Braunschweig, GermanyTWINCORE GmbH, Centre for Experimental and Clinical Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, GermanyNMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, GermanyDepartment for Rheumatology and Immunology, Hannover Medical School, Hannover, GermanyGerman Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Hannover, GermanyCiiM - Centre for Individualized Infection Medicine, Hannover, GermanyHaemodialysis 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1004045/fulldialysismRNA vaccinationOmicron variant of concernprotective immunityimmunocompromisedlongitudinal response |
| spellingShingle | Matthias Becker Anne Cossmann Karsten Lürken Daniel Junker Jens Gruber Jennifer Juengling Gema Morillas Ramos Andrea Beigel Eike Wrenger Gerhard Lonnemann Metodi V. Stankov Alexandra Dopfer-Jablonka Alexandra Dopfer-Jablonka Philipp D. Kaiser Bjoern Traenkle Ulrich Rothbauer Ulrich Rothbauer Gérard Krause Gérard Krause Gérard Krause Nicole Schneiderhan-Marra Monika Strengert Monika Strengert Alex Dulovic Georg M. N. Behrens Georg M. N. Behrens Georg M. N. Behrens Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients Frontiers in Immunology dialysis mRNA vaccination Omicron variant of concern protective immunity immunocompromised longitudinal response |
| title | Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients |
| title_full | Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients |
| title_fullStr | Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients |
| title_full_unstemmed | Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients |
| title_short | Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients |
| title_sort | longitudinal cellular and humoral immune responses after triple bnt162b2 and fourth full dose mrna 1273 vaccination in haemodialysis patients |
| topic | dialysis mRNA vaccination Omicron variant of concern protective immunity immunocompromised longitudinal response |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1004045/full |
| work_keys_str_mv | AT matthiasbecker longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT annecossmann longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT karstenlurken longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT danieljunker longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT jensgruber longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT jenniferjuengling longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT gemamorillasramos longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT andreabeigel longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT eikewrenger longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT gerhardlonnemann longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT metodivstankov longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT alexandradopferjablonka longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT alexandradopferjablonka longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT philippdkaiser longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT bjoerntraenkle longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT ulrichrothbauer longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT ulrichrothbauer longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT gerardkrause longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT gerardkrause longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT gerardkrause longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT nicoleschneiderhanmarra longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT monikastrengert longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT monikastrengert longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT alexdulovic longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT georgmnbehrens longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT georgmnbehrens longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients AT georgmnbehrens longitudinalcellularandhumoralimmuneresponsesaftertriplebnt162b2andfourthfulldosemrna1273vaccinationinhaemodialysispatients |