Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients
Aims Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with t...
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| Veröffentlicht in: | Clinical research in cardiology 2021-08, Vol.110 (8), p.1142-1149 |
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| creator | Schramm, René Costard-Jäckle, Angelika Rivinius, Rasmus Fischer, Bastian Müller, Benjamin Boeken, Udo Haneya, Assad Provaznik, Zdenek Knabbe, Cornelius Gummert, Jan |
| description | Aims
Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with the BNT162b2 vaccine (Pfizer-BioNTech) in cardiothoracic transplant recipients.
Methods and results
A total of 50 transplant patients [1–3 years post heart (42), lung (7), or heart–lung (1) transplant, mean age 55 ± 10 years] and a control group of 50 healthy staff members were included. Blood samples were analysed 21 days after the prime and the boosting dose, respectively, to quantify anti-SARS-CoV-2 spike protein (S) immunoglobulin titres (tested by Abbott, Euroimmun and RocheElecsys Immunoassays, each) and the functional inhibitory capacity of neutralizing antibodies (Genscript). To test for a specific T-cell response, heparinized whole blood was stimulated with SARS-CoV-2 specific peptides, covering domains of the viral spike, nucleocapsid and membrane protein, and the interferon-γ release was measured (QuantiFERON Monitor ELISA, Qiagen). The vast majority of transplant patients (90%) showed neither a detectable humoral nor a T-cell response three weeks after the completed two-dose BNT162b2 vaccination; these results are in sharp contrast to the robust immunogenicity seen in the control group: 98% exhibited seroconversion after the prime dose already, with a further significant increase of IgG titres after the booster dose (average > tenfold increase), a more than 90% inhibition capability of neutralizing antibodies as well as evidence of a T-cell responsiveness.
Conclusions
The findings of poor immune responses to a two-dose BNT162b2 vaccination in cardiothoracic transplant patients have a significant impact for organ transplant recipients specifically and possibly for immunocompromised patients in general. It urges for a review of future vaccine strategies in these patients. |
| doi_str_mv | 10.1007/s00392-021-01880-5 |
| format | Article |
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Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with the BNT162b2 vaccine (Pfizer-BioNTech) in cardiothoracic transplant recipients.
Methods and results
A total of 50 transplant patients [1–3 years post heart (42), lung (7), or heart–lung (1) transplant, mean age 55 ± 10 years] and a control group of 50 healthy staff members were included. Blood samples were analysed 21 days after the prime and the boosting dose, respectively, to quantify anti-SARS-CoV-2 spike protein (S) immunoglobulin titres (tested by Abbott, Euroimmun and RocheElecsys Immunoassays, each) and the functional inhibitory capacity of neutralizing antibodies (Genscript). To test for a specific T-cell response, heparinized whole blood was stimulated with SARS-CoV-2 specific peptides, covering domains of the viral spike, nucleocapsid and membrane protein, and the interferon-γ release was measured (QuantiFERON Monitor ELISA, Qiagen). The vast majority of transplant patients (90%) showed neither a detectable humoral nor a T-cell response three weeks after the completed two-dose BNT162b2 vaccination; these results are in sharp contrast to the robust immunogenicity seen in the control group: 98% exhibited seroconversion after the prime dose already, with a further significant increase of IgG titres after the booster dose (average > tenfold increase), a more than 90% inhibition capability of neutralizing antibodies as well as evidence of a T-cell responsiveness.
Conclusions
The findings of poor immune responses to a two-dose BNT162b2 vaccination in cardiothoracic transplant patients have a significant impact for organ transplant recipients specifically and possibly for immunocompromised patients in general. It urges for a review of future vaccine strategies in these patients.</description><identifier>ISSN: 1861-0684</identifier><identifier>EISSN: 1861-0692</identifier><identifier>DOI: 10.1007/s00392-021-01880-5</identifier><identifier>PMID: 34241676</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Antibodies ; Blood ; Cardiology ; Enzyme-linked immunosorbent assay ; Heart transplantation ; Immune response ; Immune system ; Immunoassays ; Immunocompromised hosts ; Immunogenicity ; Immunoglobulin G ; Interferon ; Lungs ; Lymphocytes T ; Medicine ; Medicine & Public Health ; Membrane proteins ; mRNA ; mRNA vaccines ; Neutralizing ; Nucleocapsids ; Original Paper ; Peptides ; Proteins ; Seroconversion ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; Spike protein ; Vaccines ; γ-Interferon</subject><ispartof>Clinical research in cardiology, 2021-08, Vol.110 (8), p.1142-1149</ispartof><rights>The Author(s) 2021</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-4083176a1fc176785fa7fdff8d87d8c2f24d11a18547fc72d19dab205a6484e63</citedby><cites>FETCH-LOGICAL-c500t-4083176a1fc176785fa7fdff8d87d8c2f24d11a18547fc72d19dab205a6484e63</cites><orcidid>0000-0003-1464-239X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00392-021-01880-5$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00392-021-01880-5$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids></links><search><creatorcontrib>Schramm, René</creatorcontrib><creatorcontrib>Costard-Jäckle, Angelika</creatorcontrib><creatorcontrib>Rivinius, Rasmus</creatorcontrib><creatorcontrib>Fischer, Bastian</creatorcontrib><creatorcontrib>Müller, Benjamin</creatorcontrib><creatorcontrib>Boeken, Udo</creatorcontrib><creatorcontrib>Haneya, Assad</creatorcontrib><creatorcontrib>Provaznik, Zdenek</creatorcontrib><creatorcontrib>Knabbe, Cornelius</creatorcontrib><creatorcontrib>Gummert, Jan</creatorcontrib><title>Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients</title><title>Clinical research in cardiology</title><addtitle>Clin Res Cardiol</addtitle><description>Aims
Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with the BNT162b2 vaccine (Pfizer-BioNTech) in cardiothoracic transplant recipients.
Methods and results
A total of 50 transplant patients [1–3 years post heart (42), lung (7), or heart–lung (1) transplant, mean age 55 ± 10 years] and a control group of 50 healthy staff members were included. Blood samples were analysed 21 days after the prime and the boosting dose, respectively, to quantify anti-SARS-CoV-2 spike protein (S) immunoglobulin titres (tested by Abbott, Euroimmun and RocheElecsys Immunoassays, each) and the functional inhibitory capacity of neutralizing antibodies (Genscript). To test for a specific T-cell response, heparinized whole blood was stimulated with SARS-CoV-2 specific peptides, covering domains of the viral spike, nucleocapsid and membrane protein, and the interferon-γ release was measured (QuantiFERON Monitor ELISA, Qiagen). The vast majority of transplant patients (90%) showed neither a detectable humoral nor a T-cell response three weeks after the completed two-dose BNT162b2 vaccination; these results are in sharp contrast to the robust immunogenicity seen in the control group: 98% exhibited seroconversion after the prime dose already, with a further significant increase of IgG titres after the booster dose (average > tenfold increase), a more than 90% inhibition capability of neutralizing antibodies as well as evidence of a T-cell responsiveness.
Conclusions
The findings of poor immune responses to a two-dose BNT162b2 vaccination in cardiothoracic transplant patients have a significant impact for organ transplant recipients specifically and possibly for immunocompromised patients in general. It urges for a review of future vaccine strategies in these patients.</description><subject>Antibodies</subject><subject>Blood</subject><subject>Cardiology</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Heart transplantation</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunoassays</subject><subject>Immunocompromised hosts</subject><subject>Immunogenicity</subject><subject>Immunoglobulin G</subject><subject>Interferon</subject><subject>Lungs</subject><subject>Lymphocytes T</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Membrane proteins</subject><subject>mRNA</subject><subject>mRNA vaccines</subject><subject>Neutralizing</subject><subject>Nucleocapsids</subject><subject>Original Paper</subject><subject>Peptides</subject><subject>Proteins</subject><subject>Seroconversion</subject><subject>Severe acute respiratory syndrome</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Spike protein</subject><subject>Vaccines</subject><subject>γ-Interferon</subject><issn>1861-0684</issn><issn>1861-0692</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kU1PXCEUholpo1b9A65IXGOBy9dsTMaJtk2MbXR0Sxg-HMwduIU7Gjf97WU6RuOmq3MI73neAy8AxwSfEozl14pxN6EIU4IwUQojvgP2iRLtKCb001uv2B74Uusjxpzgju2CvY5RRoQU--DPr5wLXK5XuZgemuTgHFnf97D4OuRUPRwzHJ8zcrn1t9ObWzTL94jCla_Vpwdf4M31FD4Za2Py8Px6TgRdUBgTtKa4mMdlI9to4VhMqkNv0tjYNg7Rp7Eegs_B9NUfvdYDcHd5MZ99R1c_v_2YTa-Q5RiPiGHVESkMCbYVqXgwMrgQlFPSKUsDZY4QQxRnMlhJHZk4s6CYG8EU86I7AGdb7rBerLyzzbu9Vw8lrkx50dlE_fEmxaV-yE9aUSGbYwOcvAJK_r32ddSPeV1S21lTzrlUtJO8qehWZUuutfjw5kCw3mSmt5nplpn-l5neDHXbodrEmx99R_9n6i8c85i5</recordid><startdate>20210801</startdate><enddate>20210801</enddate><creator>Schramm, René</creator><creator>Costard-Jäckle, Angelika</creator><creator>Rivinius, Rasmus</creator><creator>Fischer, Bastian</creator><creator>Müller, Benjamin</creator><creator>Boeken, Udo</creator><creator>Haneya, Assad</creator><creator>Provaznik, Zdenek</creator><creator>Knabbe, Cornelius</creator><creator>Gummert, Jan</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7Z</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1464-239X</orcidid></search><sort><creationdate>20210801</creationdate><title>Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients</title><author>Schramm, René ; 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Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with the BNT162b2 vaccine (Pfizer-BioNTech) in cardiothoracic transplant recipients.
Methods and results
A total of 50 transplant patients [1–3 years post heart (42), lung (7), or heart–lung (1) transplant, mean age 55 ± 10 years] and a control group of 50 healthy staff members were included. Blood samples were analysed 21 days after the prime and the boosting dose, respectively, to quantify anti-SARS-CoV-2 spike protein (S) immunoglobulin titres (tested by Abbott, Euroimmun and RocheElecsys Immunoassays, each) and the functional inhibitory capacity of neutralizing antibodies (Genscript). To test for a specific T-cell response, heparinized whole blood was stimulated with SARS-CoV-2 specific peptides, covering domains of the viral spike, nucleocapsid and membrane protein, and the interferon-γ release was measured (QuantiFERON Monitor ELISA, Qiagen). The vast majority of transplant patients (90%) showed neither a detectable humoral nor a T-cell response three weeks after the completed two-dose BNT162b2 vaccination; these results are in sharp contrast to the robust immunogenicity seen in the control group: 98% exhibited seroconversion after the prime dose already, with a further significant increase of IgG titres after the booster dose (average > tenfold increase), a more than 90% inhibition capability of neutralizing antibodies as well as evidence of a T-cell responsiveness.
Conclusions
The findings of poor immune responses to a two-dose BNT162b2 vaccination in cardiothoracic transplant patients have a significant impact for organ transplant recipients specifically and possibly for immunocompromised patients in general. It urges for a review of future vaccine strategies in these patients.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>34241676</pmid><doi>10.1007/s00392-021-01880-5</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-1464-239X</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Springer Nature - Complete Springer Journals |
| subjects | Antibodies Blood Cardiology Enzyme-linked immunosorbent assay Heart transplantation Immune response Immune system Immunoassays Immunocompromised hosts Immunogenicity Immunoglobulin G Interferon Lungs Lymphocytes T Medicine Medicine & Public Health Membrane proteins mRNA mRNA vaccines Neutralizing Nucleocapsids Original Paper Peptides Proteins Seroconversion Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 Spike protein Vaccines γ-Interferon |
| title | Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients |
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