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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 |
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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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fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2555348128</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/cid/ciab656</oup_id><sourcerecordid>2555348128</sourcerecordid><originalsourceid>FETCH-LOGICAL-c357t-d39daf88c1f3665a12639d9bbca75d8e971d3f328a12b6120d4f1f2a876b67113</originalsourceid><addsrcrecordid>eNp9kUGP1CAYhhujcdfVk3fzncxMNtVSCqXHbmddJ1mzyVTn2lCgiplCBbpJ_7c_QMYZTbx4IBB48nwveZPkNcreoazC74WWcfGeEvokuUQElyklFXoazxlhacEwu0heeP89yxBiGXmeXOACZxUt2GXycztOXASwA7TqUTkFtZiDgp3yk3Y8WLdAuxjp7Kigsc4a_qjd7CGHVVvv2rSx-zRfw547zU1Ia-9tDBOUjAqhpiiAG22kNl9hY0euDax2N5s1fJoDD9oaD9ZA-Kagnf2R170-6LBAsDGQm0eoTbyzUisPtwct9FHdL_9k2WivuFeQZ6iCVfOw325SVK1hawYljkMgpthzIbT5PfNl8mzgB69enfer5MuH28_Nx_T-4W7b1PepwKQMqcSV5ANjAg2YUsJRTuNN1feCl0QyVZVI4gHnLL70FOWZLAY05JyVtKclQvgqWZ28k7M_ZuVDN-r4ycOBG2Vn3-WEEFwwlLOIXp9Q4az3Tg3d5PTI3dKhrDvW3MWau3PNkX5zFs_9qORf9k-vEXh7Auw8_df0Cx43src</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2555348128</pqid></control><display><type>article</type><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><source>Oxford Journals - Connect here FIRST to enable access</source><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</creator><creatorcontrib>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</creatorcontrib><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><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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