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Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant-Associated Receptor Binding Domain (RBD) Mutations on the Susceptibility to Serum Antibodies Elicited by Coronavirus Disease 2019 (COVID-19) Infection or Vaccination

Abstract Background Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages with mutations at the spike protein receptor binding domain (RBD) have reduced susceptibility to antibody neutralization, and have been classified as variants of concern (VOCs) or variants of interest (...

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Published in:Clinical infectious diseases 2022-05, Vol.74 (9), p.1623-1630
Main Authors: Chen, Lin-Lei, Lu, Lu, Choi, Charlotte Yee-Ki, Cai, Jian-Piao, Tsoi, Hoi-Wah, Chu, Allen Wing-Ho, Ip, Jonathan Daniel, Chan, Wan-Mui, Zhang, Ricky Ruiqi, Zhang, Xiaojuan, Tam, Anthony Raymond, Lau, Daphne Pui-Ling, To, Wing-Kin, Que, Tak-Lun, Yip, Cyril Chik-Yan, Chan, Kwok-Hung, Cheng, Vincent Chi-Chung, Yuen, Kwok-Yung, Hung, Ivan Fan-Ngai, To, Kelvin Kai-Wang
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cited_by cdi_FETCH-LOGICAL-c357t-d39daf88c1f3665a12639d9bbca75d8e971d3f328a12b6120d4f1f2a876b67113
cites cdi_FETCH-LOGICAL-c357t-d39daf88c1f3665a12639d9bbca75d8e971d3f328a12b6120d4f1f2a876b67113
container_end_page 1630
container_issue 9
container_start_page 1623
container_title Clinical infectious diseases
container_volume 74
creator Chen, Lin-Lei
Lu, Lu
Choi, Charlotte Yee-Ki
Cai, Jian-Piao
Tsoi, Hoi-Wah
Chu, Allen Wing-Ho
Ip, Jonathan Daniel
Chan, Wan-Mui
Zhang, Ricky Ruiqi
Zhang, Xiaojuan
Tam, Anthony Raymond
Lau, Daphne Pui-Ling
To, Wing-Kin
Que, Tak-Lun
Yip, Cyril Chik-Yan
Chan, Kwok-Hung
Cheng, Vincent Chi-Chung
Yuen, Kwok-Yung
Hung, Ivan Fan-Ngai
To, Kelvin Kai-Wang
description Abstract Background Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages with mutations at the spike protein receptor binding domain (RBD) have reduced susceptibility to antibody neutralization, and have been classified as variants of concern (VOCs) or variants of interest (VOIs). Here we systematically compared the neutralization susceptibility and RBD binding of different VOCs/VOIs, including B.1.617.1 (kappa variant) and P.3 (theta variant), which were first detected in India and the Philippines, respectively. Methods The neutralization susceptibility of the VOCs/VOIs (B.1.351, B.1.617.1, and P.3) and a non-VOC/VOI without RBD mutations (B.1.36.27) to convalescent sera from coronavirus disease 2019 (COVID-19) patients or BNT162b2 vaccinees was determined using a live virus microneutralization (MN) assay. Serum immunoglobulin G (IgG) binding to wild-type and mutant RBDs were determined using an enzyme immunoassay. Results The geometric mean neutralization titers (GMT) of B.1.351, P.3, and B.1.617.1 were significantly lower than that of B.1.36.27 for COVID-19 patients infected with non-VOCs/VOIs (3.4- to 5.7-fold lower) or individuals who have received 2 doses of BNT162b2 vaccine (4.4- to 7.3-fold lower). The GMT of B.1.351 or P.3 were lower than that of B.1.617.1. For the 4 patients infected with B.1.351 or B.1.617.1, the MN titer was highest for their respective lineage. RBD with E484K or E484Q mutation, either alone or in combination with other mutations, showed greatest reduction in serum IgG binding. Conclusions P.3 and B.1.617.1 escape serum neutralization induced by natural infection or vaccine. Infection with 1 variant does not confer cross-protection for heterologous lineages. Immunogenicity testing for second generation COVID-19 vaccines should include multiple variant and “nonvariant” strains. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) theta (P.3) and kappa (B.1.617.1) variants can escape convalescent serum and vaccine-induced serum neutralizing response. The spike E484K mutation has the greatest impact on receptor binding domain (RBD) binding.
doi_str_mv 10.1093/cid/ciab656
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Here we systematically compared the neutralization susceptibility and RBD binding of different VOCs/VOIs, including B.1.617.1 (kappa variant) and P.3 (theta variant), which were first detected in India and the Philippines, respectively. Methods The neutralization susceptibility of the VOCs/VOIs (B.1.351, B.1.617.1, and P.3) and a non-VOC/VOI without RBD mutations (B.1.36.27) to convalescent sera from coronavirus disease 2019 (COVID-19) patients or BNT162b2 vaccinees was determined using a live virus microneutralization (MN) assay. Serum immunoglobulin G (IgG) binding to wild-type and mutant RBDs were determined using an enzyme immunoassay. Results The geometric mean neutralization titers (GMT) of B.1.351, P.3, and B.1.617.1 were significantly lower than that of B.1.36.27 for COVID-19 patients infected with non-VOCs/VOIs (3.4- to 5.7-fold lower) or individuals who have received 2 doses of BNT162b2 vaccine (4.4- to 7.3-fold lower). The GMT of B.1.351 or P.3 were lower than that of B.1.617.1. For the 4 patients infected with B.1.351 or B.1.617.1, the MN titer was highest for their respective lineage. RBD with E484K or E484Q mutation, either alone or in combination with other mutations, showed greatest reduction in serum IgG binding. Conclusions P.3 and B.1.617.1 escape serum neutralization induced by natural infection or vaccine. Infection with 1 variant does not confer cross-protection for heterologous lineages. Immunogenicity testing for second generation COVID-19 vaccines should include multiple variant and “nonvariant” strains. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) theta (P.3) and kappa (B.1.617.1) variants can escape convalescent serum and vaccine-induced serum neutralizing response. The spike E484K mutation has the greatest impact on receptor binding domain (RBD) binding.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1093/cid/ciab656</identifier><identifier>PMID: 34309648</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Antibodies, Neutralizing ; Antibodies, Viral ; BNT162 Vaccine ; COVID-19 - therapy ; COVID-19 Vaccines ; Humans ; Immunization, Passive ; Immunoglobulin G ; Mutation ; SARS-CoV-2 - genetics ; Spike Glycoprotein, Coronavirus - genetics ; Spike Glycoprotein, Coronavirus - metabolism ; Vaccination</subject><ispartof>Clinical infectious diseases, 2022-05, Vol.74 (9), p.1623-1630</ispartof><rights>The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c357t-d39daf88c1f3665a12639d9bbca75d8e971d3f328a12b6120d4f1f2a876b67113</citedby><cites>FETCH-LOGICAL-c357t-d39daf88c1f3665a12639d9bbca75d8e971d3f328a12b6120d4f1f2a876b67113</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,1591,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34309648$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Lin-Lei</creatorcontrib><creatorcontrib>Lu, Lu</creatorcontrib><creatorcontrib>Choi, Charlotte Yee-Ki</creatorcontrib><creatorcontrib>Cai, Jian-Piao</creatorcontrib><creatorcontrib>Tsoi, Hoi-Wah</creatorcontrib><creatorcontrib>Chu, Allen Wing-Ho</creatorcontrib><creatorcontrib>Ip, Jonathan Daniel</creatorcontrib><creatorcontrib>Chan, Wan-Mui</creatorcontrib><creatorcontrib>Zhang, Ricky Ruiqi</creatorcontrib><creatorcontrib>Zhang, Xiaojuan</creatorcontrib><creatorcontrib>Tam, Anthony Raymond</creatorcontrib><creatorcontrib>Lau, Daphne Pui-Ling</creatorcontrib><creatorcontrib>To, Wing-Kin</creatorcontrib><creatorcontrib>Que, Tak-Lun</creatorcontrib><creatorcontrib>Yip, Cyril Chik-Yan</creatorcontrib><creatorcontrib>Chan, Kwok-Hung</creatorcontrib><creatorcontrib>Cheng, Vincent Chi-Chung</creatorcontrib><creatorcontrib>Yuen, Kwok-Yung</creatorcontrib><creatorcontrib>Hung, Ivan Fan-Ngai</creatorcontrib><creatorcontrib>To, Kelvin Kai-Wang</creatorcontrib><title>Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant-Associated Receptor Binding Domain (RBD) Mutations on the Susceptibility to Serum Antibodies Elicited by Coronavirus Disease 2019 (COVID-19) Infection or Vaccination</title><title>Clinical infectious diseases</title><addtitle>Clin Infect Dis</addtitle><description>Abstract Background Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages with mutations at the spike protein receptor binding domain (RBD) have reduced susceptibility to antibody neutralization, and have been classified as variants of concern (VOCs) or variants of interest (VOIs). Here we systematically compared the neutralization susceptibility and RBD binding of different VOCs/VOIs, including B.1.617.1 (kappa variant) and P.3 (theta variant), which were first detected in India and the Philippines, respectively. Methods The neutralization susceptibility of the VOCs/VOIs (B.1.351, B.1.617.1, and P.3) and a non-VOC/VOI without RBD mutations (B.1.36.27) to convalescent sera from coronavirus disease 2019 (COVID-19) patients or BNT162b2 vaccinees was determined using a live virus microneutralization (MN) assay. Serum immunoglobulin G (IgG) binding to wild-type and mutant RBDs were determined using an enzyme immunoassay. Results The geometric mean neutralization titers (GMT) of B.1.351, P.3, and B.1.617.1 were significantly lower than that of B.1.36.27 for COVID-19 patients infected with non-VOCs/VOIs (3.4- to 5.7-fold lower) or individuals who have received 2 doses of BNT162b2 vaccine (4.4- to 7.3-fold lower). The GMT of B.1.351 or P.3 were lower than that of B.1.617.1. For the 4 patients infected with B.1.351 or B.1.617.1, the MN titer was highest for their respective lineage. RBD with E484K or E484Q mutation, either alone or in combination with other mutations, showed greatest reduction in serum IgG binding. Conclusions P.3 and B.1.617.1 escape serum neutralization induced by natural infection or vaccine. Infection with 1 variant does not confer cross-protection for heterologous lineages. Immunogenicity testing for second generation COVID-19 vaccines should include multiple variant and “nonvariant” strains. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) theta (P.3) and kappa (B.1.617.1) variants can escape convalescent serum and vaccine-induced serum neutralizing response. The spike E484K mutation has the greatest impact on receptor binding domain (RBD) binding.</description><subject>Antibodies, Neutralizing</subject><subject>Antibodies, Viral</subject><subject>BNT162 Vaccine</subject><subject>COVID-19 - therapy</subject><subject>COVID-19 Vaccines</subject><subject>Humans</subject><subject>Immunization, Passive</subject><subject>Immunoglobulin G</subject><subject>Mutation</subject><subject>SARS-CoV-2 - genetics</subject><subject>Spike Glycoprotein, Coronavirus - genetics</subject><subject>Spike Glycoprotein, Coronavirus - metabolism</subject><subject>Vaccination</subject><issn>1058-4838</issn><issn>1537-6591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kUGP1CAYhhujcdfVk3fzncxMNtVSCqXHbmddJ1mzyVTn2lCgiplCBbpJ_7c_QMYZTbx4IBB48nwveZPkNcreoazC74WWcfGeEvokuUQElyklFXoazxlhacEwu0heeP89yxBiGXmeXOACZxUt2GXycztOXASwA7TqUTkFtZiDgp3yk3Y8WLdAuxjp7Kigsc4a_qjd7CGHVVvv2rSx-zRfw547zU1Ia-9tDBOUjAqhpiiAG22kNl9hY0euDax2N5s1fJoDD9oaD9ZA-Kagnf2R170-6LBAsDGQm0eoTbyzUisPtwct9FHdL_9k2WivuFeQZ6iCVfOw325SVK1hawYljkMgpthzIbT5PfNl8mzgB69enfer5MuH28_Nx_T-4W7b1PepwKQMqcSV5ANjAg2YUsJRTuNN1feCl0QyVZVI4gHnLL70FOWZLAY05JyVtKclQvgqWZ28k7M_ZuVDN-r4ycOBG2Vn3-WEEFwwlLOIXp9Q4az3Tg3d5PTI3dKhrDvW3MWau3PNkX5zFs_9qORf9k-vEXh7Auw8_df0Cx43src</recordid><startdate>20220503</startdate><enddate>20220503</enddate><creator>Chen, Lin-Lei</creator><creator>Lu, Lu</creator><creator>Choi, Charlotte Yee-Ki</creator><creator>Cai, Jian-Piao</creator><creator>Tsoi, Hoi-Wah</creator><creator>Chu, Allen Wing-Ho</creator><creator>Ip, Jonathan Daniel</creator><creator>Chan, Wan-Mui</creator><creator>Zhang, Ricky Ruiqi</creator><creator>Zhang, Xiaojuan</creator><creator>Tam, Anthony Raymond</creator><creator>Lau, Daphne Pui-Ling</creator><creator>To, Wing-Kin</creator><creator>Que, Tak-Lun</creator><creator>Yip, Cyril Chik-Yan</creator><creator>Chan, Kwok-Hung</creator><creator>Cheng, Vincent Chi-Chung</creator><creator>Yuen, Kwok-Yung</creator><creator>Hung, Ivan Fan-Ngai</creator><creator>To, Kelvin Kai-Wang</creator><general>Oxford University Press</general><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>7X8</scope></search><sort><creationdate>20220503</creationdate><title>Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant-Associated Receptor Binding Domain (RBD) Mutations on the Susceptibility to Serum Antibodies Elicited by Coronavirus Disease 2019 (COVID-19) Infection or Vaccination</title><author>Chen, Lin-Lei ; Lu, Lu ; Choi, Charlotte Yee-Ki ; Cai, Jian-Piao ; Tsoi, Hoi-Wah ; Chu, Allen Wing-Ho ; Ip, Jonathan Daniel ; Chan, Wan-Mui ; Zhang, Ricky Ruiqi ; Zhang, Xiaojuan ; Tam, Anthony Raymond ; Lau, Daphne Pui-Ling ; To, Wing-Kin ; Que, Tak-Lun ; Yip, Cyril Chik-Yan ; Chan, Kwok-Hung ; Cheng, Vincent Chi-Chung ; Yuen, Kwok-Yung ; Hung, Ivan Fan-Ngai ; To, Kelvin Kai-Wang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c357t-d39daf88c1f3665a12639d9bbca75d8e971d3f328a12b6120d4f1f2a876b67113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antibodies, Neutralizing</topic><topic>Antibodies, Viral</topic><topic>BNT162 Vaccine</topic><topic>COVID-19 - therapy</topic><topic>COVID-19 Vaccines</topic><topic>Humans</topic><topic>Immunization, Passive</topic><topic>Immunoglobulin G</topic><topic>Mutation</topic><topic>SARS-CoV-2 - genetics</topic><topic>Spike Glycoprotein, Coronavirus - genetics</topic><topic>Spike Glycoprotein, Coronavirus - metabolism</topic><topic>Vaccination</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Lin-Lei</creatorcontrib><creatorcontrib>Lu, Lu</creatorcontrib><creatorcontrib>Choi, Charlotte Yee-Ki</creatorcontrib><creatorcontrib>Cai, Jian-Piao</creatorcontrib><creatorcontrib>Tsoi, Hoi-Wah</creatorcontrib><creatorcontrib>Chu, Allen Wing-Ho</creatorcontrib><creatorcontrib>Ip, Jonathan Daniel</creatorcontrib><creatorcontrib>Chan, Wan-Mui</creatorcontrib><creatorcontrib>Zhang, Ricky Ruiqi</creatorcontrib><creatorcontrib>Zhang, Xiaojuan</creatorcontrib><creatorcontrib>Tam, Anthony Raymond</creatorcontrib><creatorcontrib>Lau, Daphne Pui-Ling</creatorcontrib><creatorcontrib>To, Wing-Kin</creatorcontrib><creatorcontrib>Que, Tak-Lun</creatorcontrib><creatorcontrib>Yip, Cyril Chik-Yan</creatorcontrib><creatorcontrib>Chan, Kwok-Hung</creatorcontrib><creatorcontrib>Cheng, Vincent Chi-Chung</creatorcontrib><creatorcontrib>Yuen, Kwok-Yung</creatorcontrib><creatorcontrib>Hung, Ivan Fan-Ngai</creatorcontrib><creatorcontrib>To, Kelvin Kai-Wang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Lin-Lei</au><au>Lu, Lu</au><au>Choi, Charlotte Yee-Ki</au><au>Cai, Jian-Piao</au><au>Tsoi, Hoi-Wah</au><au>Chu, Allen Wing-Ho</au><au>Ip, Jonathan Daniel</au><au>Chan, Wan-Mui</au><au>Zhang, Ricky Ruiqi</au><au>Zhang, Xiaojuan</au><au>Tam, Anthony Raymond</au><au>Lau, Daphne Pui-Ling</au><au>To, Wing-Kin</au><au>Que, Tak-Lun</au><au>Yip, Cyril Chik-Yan</au><au>Chan, Kwok-Hung</au><au>Cheng, Vincent Chi-Chung</au><au>Yuen, Kwok-Yung</au><au>Hung, Ivan Fan-Ngai</au><au>To, Kelvin Kai-Wang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant-Associated Receptor Binding Domain (RBD) Mutations on the Susceptibility to Serum Antibodies Elicited by Coronavirus Disease 2019 (COVID-19) Infection or Vaccination</atitle><jtitle>Clinical infectious diseases</jtitle><addtitle>Clin Infect Dis</addtitle><date>2022-05-03</date><risdate>2022</risdate><volume>74</volume><issue>9</issue><spage>1623</spage><epage>1630</epage><pages>1623-1630</pages><issn>1058-4838</issn><eissn>1537-6591</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Abstract Background Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages with mutations at the spike protein receptor binding domain (RBD) have reduced susceptibility to antibody neutralization, and have been classified as variants of concern (VOCs) or variants of interest (VOIs). Here we systematically compared the neutralization susceptibility and RBD binding of different VOCs/VOIs, including B.1.617.1 (kappa variant) and P.3 (theta variant), which were first detected in India and the Philippines, respectively. Methods The neutralization susceptibility of the VOCs/VOIs (B.1.351, B.1.617.1, and P.3) and a non-VOC/VOI without RBD mutations (B.1.36.27) to convalescent sera from coronavirus disease 2019 (COVID-19) patients or BNT162b2 vaccinees was determined using a live virus microneutralization (MN) assay. Serum immunoglobulin G (IgG) binding to wild-type and mutant RBDs were determined using an enzyme immunoassay. Results The geometric mean neutralization titers (GMT) of B.1.351, P.3, and B.1.617.1 were significantly lower than that of B.1.36.27 for COVID-19 patients infected with non-VOCs/VOIs (3.4- to 5.7-fold lower) or individuals who have received 2 doses of BNT162b2 vaccine (4.4- to 7.3-fold lower). The GMT of B.1.351 or P.3 were lower than that of B.1.617.1. For the 4 patients infected with B.1.351 or B.1.617.1, the MN titer was highest for their respective lineage. RBD with E484K or E484Q mutation, either alone or in combination with other mutations, showed greatest reduction in serum IgG binding. Conclusions P.3 and B.1.617.1 escape serum neutralization induced by natural infection or vaccine. Infection with 1 variant does not confer cross-protection for heterologous lineages. Immunogenicity testing for second generation COVID-19 vaccines should include multiple variant and “nonvariant” strains. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) theta (P.3) and kappa (B.1.617.1) variants can escape convalescent serum and vaccine-induced serum neutralizing response. The spike E484K mutation has the greatest impact on receptor binding domain (RBD) binding.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>34309648</pmid><doi>10.1093/cid/ciab656</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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source Oxford Journals - Connect here FIRST to enable access
subjects Antibodies, Neutralizing
Antibodies, Viral
BNT162 Vaccine
COVID-19 - therapy
COVID-19 Vaccines
Humans
Immunization, Passive
Immunoglobulin G
Mutation
SARS-CoV-2 - genetics
Spike Glycoprotein, Coronavirus - genetics
Spike Glycoprotein, Coronavirus - metabolism
Vaccination
title Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant-Associated Receptor Binding Domain (RBD) Mutations on the Susceptibility to Serum Antibodies Elicited by Coronavirus Disease 2019 (COVID-19) Infection or Vaccination
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