SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: Everybody Does their Best
Background Data on immune responses to SARS-CoV-2 in patients with Primary Antibody Deficiencies (PAD) are limited to infected patients and to heterogeneous cohorts after immunization. Methods Forty-one patients with Common Variable Immune Deficiencies (CVID), six patients with X-linked Agammaglobul...
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| Veröffentlicht in: | Journal of clinical immunology 2021-11, Vol.41 (8), p.1709-1722 |
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| creator | Salinas, Ane Fernandez Mortari, Eva Piano Terreri, Sara Quintarelli, Concetta Pulvirenti, Federica Di Cecca, Stefano Guercio, Marika Milito, Cinzia Bonanni, Livia Auria, Stefania Romaggioli, Laura Cusano, Giuseppina Albano, Christian Zaffina, Salvatore Perno, Carlo Federico Spadaro, Giuseppe Locatelli, Franco Carsetti, Rita Quinti, Isabella |
| description | Background
Data on immune responses to SARS-CoV-2 in patients with Primary Antibody Deficiencies (PAD) are limited to infected patients and to heterogeneous cohorts after immunization.
Methods
Forty-one patients with Common Variable Immune Deficiencies (CVID), six patients with X-linked Agammaglobulinemia (XLA), and 28 healthy age-matched controls (HD) were analyzed for anti-Spike and anti-receptor binding domain (RBD) antibody production, generation of Spike-specific memory B-cells, and Spike-specific T-cells before vaccination and one week after the second dose of BNT162b2 vaccine.
Results
The vaccine induced Spike-specific IgG and IgA antibody responses in all HD and in 20% of SARS-CoV-2 naive CVID patients. Anti-Spike IgG were detectable before vaccination in 4 out 7 CVID previously infected with SARS-CoV-2 and were boosted in six out of seven patients by the subsequent immunization raising higher levels than patients naïve to infection. While HD generated Spike-specific memory B-cells, and RBD-specific B-cells, CVID generated Spike-specific atypical B-cells, while RBD-specific B-cells were undetectable in all patients, indicating the incapability to generate this new specificity. Specific T-cell responses were evident in all HD and defective in 30% of CVID. All but one patient with XLA responded by specific T-cell only.
Conclusion
In PAD patients, early atypical immune responses after BNT162b2 immunization occurred, possibly by extra-follicular or incomplete germinal center reactions. If these responses to vaccination might result in a partial protection from infection or reinfection is now unknown. Our data suggests that SARS-CoV-2 infection more effectively primes the immune response than the immunization alone, possibly suggesting the need for a third vaccine dose for patients not previously infected. |
| doi_str_mv | 10.1007/s10875-021-01133-0 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8527979</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2584013557</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-3bfc4ecb6ef42b53c99d8e424005331d18dbfbdcdc9e667b70b8dd502bf6d7c33</originalsourceid><addsrcrecordid>eNp9kU1v1DAQhi0EotuFP8ABReLCxeDPOOGAtCwFVqqE1EKvVmxPWleJvbWTSvvvcUkpHwdOlt555vXMvAi9oOQNJUS9zZQ0SmLCKCaUco7JI7SiUnHMZMseoxVhiuKWCnaEjnO-JoTwmsmn6IiLui66WCF7vjk7x9t4gVl10VnrA1S74GYLrtpMh7233VDtxnEu-hnkfQwZcuVDtQmTN9Edqo_Qg53yu-rkFtJhkWJhpivwqfoAeXqGnvTdkOH5_btG3z-dfNt-wadfP--2m1NshRIT5qa3AqypoRfMSG7b1jUgmCBEck4dbZzpjbPOtlDXyihiGuckYaavnbKcr9H7xXc_mxGchTClbtD75McuHXTsvP67EvyVvoy3upFMtaotBq_vDVK8mcvkevTZwjB0AeKcNZONIJTLcuI1evUPeh3nFMp6hWpbphSholBsoWyKOSfoH4ahRN9lqJcMdclQ_8xQk9L08s81Hlp-hVYAvgC5lMIlpN9__8f2B5VYp7w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2599277014</pqid></control><display><type>article</type><title>SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: Everybody Does their Best</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Salinas, Ane Fernandez ; Mortari, Eva Piano ; Terreri, Sara ; Quintarelli, Concetta ; Pulvirenti, Federica ; Di Cecca, Stefano ; Guercio, Marika ; Milito, Cinzia ; Bonanni, Livia ; Auria, Stefania ; Romaggioli, Laura ; Cusano, Giuseppina ; Albano, Christian ; Zaffina, Salvatore ; Perno, Carlo Federico ; Spadaro, Giuseppe ; Locatelli, Franco ; Carsetti, Rita ; Quinti, Isabella</creator><creatorcontrib>Salinas, Ane Fernandez ; Mortari, Eva Piano ; Terreri, Sara ; Quintarelli, Concetta ; Pulvirenti, Federica ; Di Cecca, Stefano ; Guercio, Marika ; Milito, Cinzia ; Bonanni, Livia ; Auria, Stefania ; Romaggioli, Laura ; Cusano, Giuseppina ; Albano, Christian ; Zaffina, Salvatore ; Perno, Carlo Federico ; Spadaro, Giuseppe ; Locatelli, Franco ; Carsetti, Rita ; Quinti, Isabella</creatorcontrib><description>Background
Data on immune responses to SARS-CoV-2 in patients with Primary Antibody Deficiencies (PAD) are limited to infected patients and to heterogeneous cohorts after immunization.
Methods
Forty-one patients with Common Variable Immune Deficiencies (CVID), six patients with X-linked Agammaglobulinemia (XLA), and 28 healthy age-matched controls (HD) were analyzed for anti-Spike and anti-receptor binding domain (RBD) antibody production, generation of Spike-specific memory B-cells, and Spike-specific T-cells before vaccination and one week after the second dose of BNT162b2 vaccine.
Results
The vaccine induced Spike-specific IgG and IgA antibody responses in all HD and in 20% of SARS-CoV-2 naive CVID patients. Anti-Spike IgG were detectable before vaccination in 4 out 7 CVID previously infected with SARS-CoV-2 and were boosted in six out of seven patients by the subsequent immunization raising higher levels than patients naïve to infection. While HD generated Spike-specific memory B-cells, and RBD-specific B-cells, CVID generated Spike-specific atypical B-cells, while RBD-specific B-cells were undetectable in all patients, indicating the incapability to generate this new specificity. Specific T-cell responses were evident in all HD and defective in 30% of CVID. All but one patient with XLA responded by specific T-cell only.
Conclusion
In PAD patients, early atypical immune responses after BNT162b2 immunization occurred, possibly by extra-follicular or incomplete germinal center reactions. If these responses to vaccination might result in a partial protection from infection or reinfection is now unknown. Our data suggests that SARS-CoV-2 infection more effectively primes the immune response than the immunization alone, possibly suggesting the need for a third vaccine dose for patients not previously infected.</description><identifier>ISSN: 0271-9142</identifier><identifier>EISSN: 1573-2592</identifier><identifier>DOI: 10.1007/s10875-021-01133-0</identifier><identifier>PMID: 34669144</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Agammaglobulinemia ; Antibodies ; Antibodies, Viral - blood ; Biomedical and Life Sciences ; Biomedicine ; COVID-19 - prevention & control ; COVID-19 Vaccines - immunology ; Humans ; Immune response ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin G - blood ; Immunologic Deficiency Syndromes - immunology ; Immunologic Memory ; Immunological memory ; Immunology ; Infections ; Infectious Diseases ; Internal Medicine ; Lymphocytes - immunology ; Lymphocytes B ; Lymphocytes T ; Medical Microbiology ; Memory cells ; Original ; Original Article ; SARS-CoV-2 - immunology ; Severe acute respiratory syndrome coronavirus 2 ; Spike Glycoprotein, Coronavirus - immunology ; Vaccination ; Vaccines ; X-linked agammaglobulinemia</subject><ispartof>Journal of clinical immunology, 2021-11, Vol.41 (8), p.1709-1722</ispartof><rights>The Author(s) 2021</rights><rights>2021. The Author(s).</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-c474t-3bfc4ecb6ef42b53c99d8e424005331d18dbfbdcdc9e667b70b8dd502bf6d7c33</citedby><cites>FETCH-LOGICAL-c474t-3bfc4ecb6ef42b53c99d8e424005331d18dbfbdcdc9e667b70b8dd502bf6d7c33</cites><orcidid>0000-0002-3328-7584</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/s10875-021-01133-0$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10875-021-01133-0$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34669144$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Salinas, Ane Fernandez</creatorcontrib><creatorcontrib>Mortari, Eva Piano</creatorcontrib><creatorcontrib>Terreri, Sara</creatorcontrib><creatorcontrib>Quintarelli, Concetta</creatorcontrib><creatorcontrib>Pulvirenti, Federica</creatorcontrib><creatorcontrib>Di Cecca, Stefano</creatorcontrib><creatorcontrib>Guercio, Marika</creatorcontrib><creatorcontrib>Milito, Cinzia</creatorcontrib><creatorcontrib>Bonanni, Livia</creatorcontrib><creatorcontrib>Auria, Stefania</creatorcontrib><creatorcontrib>Romaggioli, Laura</creatorcontrib><creatorcontrib>Cusano, Giuseppina</creatorcontrib><creatorcontrib>Albano, Christian</creatorcontrib><creatorcontrib>Zaffina, Salvatore</creatorcontrib><creatorcontrib>Perno, Carlo Federico</creatorcontrib><creatorcontrib>Spadaro, Giuseppe</creatorcontrib><creatorcontrib>Locatelli, Franco</creatorcontrib><creatorcontrib>Carsetti, Rita</creatorcontrib><creatorcontrib>Quinti, Isabella</creatorcontrib><title>SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: Everybody Does their Best</title><title>Journal of clinical immunology</title><addtitle>J Clin Immunol</addtitle><addtitle>J Clin Immunol</addtitle><description>Background
Data on immune responses to SARS-CoV-2 in patients with Primary Antibody Deficiencies (PAD) are limited to infected patients and to heterogeneous cohorts after immunization.
Methods
Forty-one patients with Common Variable Immune Deficiencies (CVID), six patients with X-linked Agammaglobulinemia (XLA), and 28 healthy age-matched controls (HD) were analyzed for anti-Spike and anti-receptor binding domain (RBD) antibody production, generation of Spike-specific memory B-cells, and Spike-specific T-cells before vaccination and one week after the second dose of BNT162b2 vaccine.
Results
The vaccine induced Spike-specific IgG and IgA antibody responses in all HD and in 20% of SARS-CoV-2 naive CVID patients. Anti-Spike IgG were detectable before vaccination in 4 out 7 CVID previously infected with SARS-CoV-2 and were boosted in six out of seven patients by the subsequent immunization raising higher levels than patients naïve to infection. While HD generated Spike-specific memory B-cells, and RBD-specific B-cells, CVID generated Spike-specific atypical B-cells, while RBD-specific B-cells were undetectable in all patients, indicating the incapability to generate this new specificity. Specific T-cell responses were evident in all HD and defective in 30% of CVID. All but one patient with XLA responded by specific T-cell only.
Conclusion
In PAD patients, early atypical immune responses after BNT162b2 immunization occurred, possibly by extra-follicular or incomplete germinal center reactions. If these responses to vaccination might result in a partial protection from infection or reinfection is now unknown. Our data suggests that SARS-CoV-2 infection more effectively primes the immune response than the immunization alone, possibly suggesting the need for a third vaccine dose for patients not previously infected.</description><subject>Agammaglobulinemia</subject><subject>Antibodies</subject><subject>Antibodies, Viral - blood</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>COVID-19 - prevention & control</subject><subject>COVID-19 Vaccines - immunology</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunoglobulin A</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - blood</subject><subject>Immunologic Deficiency Syndromes - immunology</subject><subject>Immunologic Memory</subject><subject>Immunological memory</subject><subject>Immunology</subject><subject>Infections</subject><subject>Infectious Diseases</subject><subject>Internal Medicine</subject><subject>Lymphocytes - immunology</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Medical Microbiology</subject><subject>Memory cells</subject><subject>Original</subject><subject>Original Article</subject><subject>SARS-CoV-2 - immunology</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Spike Glycoprotein, Coronavirus - immunology</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>X-linked agammaglobulinemia</subject><issn>0271-9142</issn><issn>1573-2592</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kU1v1DAQhi0EotuFP8ABReLCxeDPOOGAtCwFVqqE1EKvVmxPWleJvbWTSvvvcUkpHwdOlt555vXMvAi9oOQNJUS9zZQ0SmLCKCaUco7JI7SiUnHMZMseoxVhiuKWCnaEjnO-JoTwmsmn6IiLui66WCF7vjk7x9t4gVl10VnrA1S74GYLrtpMh7233VDtxnEu-hnkfQwZcuVDtQmTN9Edqo_Qg53yu-rkFtJhkWJhpivwqfoAeXqGnvTdkOH5_btG3z-dfNt-wadfP--2m1NshRIT5qa3AqypoRfMSG7b1jUgmCBEck4dbZzpjbPOtlDXyihiGuckYaavnbKcr9H7xXc_mxGchTClbtD75McuHXTsvP67EvyVvoy3upFMtaotBq_vDVK8mcvkevTZwjB0AeKcNZONIJTLcuI1evUPeh3nFMp6hWpbphSholBsoWyKOSfoH4ahRN9lqJcMdclQ_8xQk9L08s81Hlp-hVYAvgC5lMIlpN9__8f2B5VYp7w</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Salinas, Ane Fernandez</creator><creator>Mortari, Eva Piano</creator><creator>Terreri, Sara</creator><creator>Quintarelli, Concetta</creator><creator>Pulvirenti, Federica</creator><creator>Di Cecca, Stefano</creator><creator>Guercio, Marika</creator><creator>Milito, Cinzia</creator><creator>Bonanni, Livia</creator><creator>Auria, Stefania</creator><creator>Romaggioli, Laura</creator><creator>Cusano, Giuseppina</creator><creator>Albano, Christian</creator><creator>Zaffina, Salvatore</creator><creator>Perno, Carlo Federico</creator><creator>Spadaro, Giuseppe</creator><creator>Locatelli, Franco</creator><creator>Carsetti, Rita</creator><creator>Quinti, Isabella</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3328-7584</orcidid></search><sort><creationdate>20211101</creationdate><title>SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: Everybody Does their Best</title><author>Salinas, Ane Fernandez ; Mortari, Eva Piano ; Terreri, Sara ; Quintarelli, Concetta ; Pulvirenti, Federica ; Di Cecca, Stefano ; Guercio, Marika ; Milito, Cinzia ; Bonanni, Livia ; Auria, Stefania ; Romaggioli, Laura ; Cusano, Giuseppina ; Albano, Christian ; Zaffina, Salvatore ; Perno, Carlo Federico ; Spadaro, Giuseppe ; Locatelli, Franco ; Carsetti, Rita ; Quinti, Isabella</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-3bfc4ecb6ef42b53c99d8e424005331d18dbfbdcdc9e667b70b8dd502bf6d7c33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Agammaglobulinemia</topic><topic>Antibodies</topic><topic>Antibodies, Viral - blood</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>COVID-19 - prevention & control</topic><topic>COVID-19 Vaccines - immunology</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immunoglobulin A</topic><topic>Immunoglobulin G</topic><topic>Immunoglobulin G - blood</topic><topic>Immunologic Deficiency Syndromes - immunology</topic><topic>Immunologic Memory</topic><topic>Immunological memory</topic><topic>Immunology</topic><topic>Infections</topic><topic>Infectious Diseases</topic><topic>Internal Medicine</topic><topic>Lymphocytes - immunology</topic><topic>Lymphocytes B</topic><topic>Lymphocytes T</topic><topic>Medical Microbiology</topic><topic>Memory cells</topic><topic>Original</topic><topic>Original Article</topic><topic>SARS-CoV-2 - immunology</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Spike Glycoprotein, Coronavirus - immunology</topic><topic>Vaccination</topic><topic>Vaccines</topic><topic>X-linked agammaglobulinemia</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Salinas, Ane Fernandez</creatorcontrib><creatorcontrib>Mortari, Eva Piano</creatorcontrib><creatorcontrib>Terreri, Sara</creatorcontrib><creatorcontrib>Quintarelli, Concetta</creatorcontrib><creatorcontrib>Pulvirenti, Federica</creatorcontrib><creatorcontrib>Di Cecca, Stefano</creatorcontrib><creatorcontrib>Guercio, Marika</creatorcontrib><creatorcontrib>Milito, Cinzia</creatorcontrib><creatorcontrib>Bonanni, Livia</creatorcontrib><creatorcontrib>Auria, Stefania</creatorcontrib><creatorcontrib>Romaggioli, Laura</creatorcontrib><creatorcontrib>Cusano, Giuseppina</creatorcontrib><creatorcontrib>Albano, Christian</creatorcontrib><creatorcontrib>Zaffina, Salvatore</creatorcontrib><creatorcontrib>Perno, Carlo Federico</creatorcontrib><creatorcontrib>Spadaro, Giuseppe</creatorcontrib><creatorcontrib>Locatelli, Franco</creatorcontrib><creatorcontrib>Carsetti, Rita</creatorcontrib><creatorcontrib>Quinti, Isabella</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of clinical immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Salinas, Ane Fernandez</au><au>Mortari, Eva Piano</au><au>Terreri, Sara</au><au>Quintarelli, Concetta</au><au>Pulvirenti, Federica</au><au>Di Cecca, Stefano</au><au>Guercio, Marika</au><au>Milito, Cinzia</au><au>Bonanni, Livia</au><au>Auria, Stefania</au><au>Romaggioli, Laura</au><au>Cusano, Giuseppina</au><au>Albano, Christian</au><au>Zaffina, Salvatore</au><au>Perno, Carlo Federico</au><au>Spadaro, Giuseppe</au><au>Locatelli, Franco</au><au>Carsetti, Rita</au><au>Quinti, Isabella</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: Everybody Does their Best</atitle><jtitle>Journal of clinical immunology</jtitle><stitle>J Clin Immunol</stitle><addtitle>J Clin Immunol</addtitle><date>2021-11-01</date><risdate>2021</risdate><volume>41</volume><issue>8</issue><spage>1709</spage><epage>1722</epage><pages>1709-1722</pages><issn>0271-9142</issn><eissn>1573-2592</eissn><abstract>Background
Data on immune responses to SARS-CoV-2 in patients with Primary Antibody Deficiencies (PAD) are limited to infected patients and to heterogeneous cohorts after immunization.
Methods
Forty-one patients with Common Variable Immune Deficiencies (CVID), six patients with X-linked Agammaglobulinemia (XLA), and 28 healthy age-matched controls (HD) were analyzed for anti-Spike and anti-receptor binding domain (RBD) antibody production, generation of Spike-specific memory B-cells, and Spike-specific T-cells before vaccination and one week after the second dose of BNT162b2 vaccine.
Results
The vaccine induced Spike-specific IgG and IgA antibody responses in all HD and in 20% of SARS-CoV-2 naive CVID patients. Anti-Spike IgG were detectable before vaccination in 4 out 7 CVID previously infected with SARS-CoV-2 and were boosted in six out of seven patients by the subsequent immunization raising higher levels than patients naïve to infection. While HD generated Spike-specific memory B-cells, and RBD-specific B-cells, CVID generated Spike-specific atypical B-cells, while RBD-specific B-cells were undetectable in all patients, indicating the incapability to generate this new specificity. Specific T-cell responses were evident in all HD and defective in 30% of CVID. All but one patient with XLA responded by specific T-cell only.
Conclusion
In PAD patients, early atypical immune responses after BNT162b2 immunization occurred, possibly by extra-follicular or incomplete germinal center reactions. If these responses to vaccination might result in a partial protection from infection or reinfection is now unknown. Our data suggests that SARS-CoV-2 infection more effectively primes the immune response than the immunization alone, possibly suggesting the need for a third vaccine dose for patients not previously infected.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>34669144</pmid><doi>10.1007/s10875-021-01133-0</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-3328-7584</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0271-9142 |
| ispartof | Journal of clinical immunology, 2021-11, Vol.41 (8), p.1709-1722 |
| issn | 0271-9142 1573-2592 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8527979 |
| source | MEDLINE; SpringerLink Journals |
| subjects | Agammaglobulinemia Antibodies Antibodies, Viral - blood Biomedical and Life Sciences Biomedicine COVID-19 - prevention & control COVID-19 Vaccines - immunology Humans Immune response Immunoglobulin A Immunoglobulin G Immunoglobulin G - blood Immunologic Deficiency Syndromes - immunology Immunologic Memory Immunological memory Immunology Infections Infectious Diseases Internal Medicine Lymphocytes - immunology Lymphocytes B Lymphocytes T Medical Microbiology Memory cells Original Original Article SARS-CoV-2 - immunology Severe acute respiratory syndrome coronavirus 2 Spike Glycoprotein, Coronavirus - immunology Vaccination Vaccines X-linked agammaglobulinemia |
| title | SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: Everybody Does their Best |
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