Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants

The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly...

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Published in	Cell Vol. 186; no. 2; pp. 279 - 286.e8
Main Authors	Wang, Qian, Iketani, Sho, Li, Zhiteng, Liu, Liyuan, Guo, Yicheng, Huang, Yiming, Bowen, Anthony D., Liu, Michael, Wang, Maple, Yu, Jian, Valdez, Riccardo, Lauring, Adam S., Sheng, Zizhang, Wang, Harris H., Gordon, Aubree, Liu, Lihong, Ho, David D.
Format	Journal Article
Language	English
Published	United States Elsevier Inc 19.01.2023 The Author(s). Published by Elsevier Inc
Subjects	antibodies Antibodies, Monoclonal Antibodies, Neutralizing Antibodies, Viral antibody evasion BQ.1 BQ.1.1 COVID-19 COVID-19 - immunology COVID-19 - virology COVID-19 infection COVID-19 Vaccines Humans Immune Evasion mRNA vaccine neutralization neutralizing monoclonal antibody receptor binding affinity SARS-CoV-2 SARS-CoV-2 - classification SARS-CoV-2 - genetics Severe acute respiratory syndrome coronavirus 2 vaccines XBB XBB.1 COVID-19 receptor binding affinity SARS-CoV-2 neutralizing monoclonal antibody XBB antibody evasion XBB.1 BQ.1 BQ.1.1 mRNA vaccine
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Abstract	The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against BQ and XBB subvariants were lower by 13- to 81-fold and 66- to 155-fold, respectively, far beyond what had been observed to date. Monoclonal antibodies capable of neutralizing the original Omicron variant were largely inactive against these new subvariants, and the responsible individual spike mutations were identified. These subvariants were found to have similar ACE2-binding affinities as their predecessors. Together, our findings indicate that BQ and XBB subvariants present serious threats to current COVID-19 vaccines, render inactive all authorized antibodies, and may have gained dominance in the population because of their advantage in evading antibodies. [Display omitted] •BQ.1, BQ.1.1, XBB, and XBB.1 are the most resistant SARS-CoV-2 variants to date•Serum neutralization was markedly reduced, including with the bivalent booster•All clinical monoclonal antibodies were rendered inactive against these variants•The ACE2 affinity of these variants were similar to their parental strains Recent BQ and XBB subvariants of SARS-CoV-2 demonstrate dramatically increased ability to evade neutralizing antibodies, even those from people who received the bivalent mRNA booster or who are immunized and had previous breakthrough Omicron infection. Additionally, both BQ and XBB are completely resistant to bebtelovimab, meaning there are now no clinically authorized therapeutic antibodies effective against these circulating variants.
AbstractList	The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against BQ and XBB subvariants were lower by 13- to 81-fold and 66- to 155-fold, respectively, far beyond what had been observed to date. Monoclonal antibodies capable of neutralizing the original Omicron variant were largely inactive against these new subvariants, and the responsible individual spike mutations were identified. These subvariants were found to have similar ACE2-binding affinities as their predecessors. Together, our findings indicate that BQ and XBB subvariants present serious threats to current COVID-19 vaccines, render inactive all authorized antibodies, and may have gained dominance in the population because of their advantage in evading antibodies. The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against BQ and XBB subvariants were lower by 13-81-fold and 66-155-fold, respectively, far beyond what had been observed to date. Monoclonal antibodies capable of neutralizing the original Omicron variant were largely inactive against these new subvariants, and the responsible individual spike mutations were identified. These subvariants were found to have similar ACE2-binding affinities as their predecessors. Together, our findings indicate that BQ and XBB subvariants present serious threats to current COVID-19 vaccines, render inactive all authorized antibodies, and may have gained dominance in the population because of their advantage in evading antibodies. Recent BQ and XBB subvariants of SARS-CoV-2 demonstrate dramatically increased ability to evade neutralizing antibodies, even those from people who received the bivalent mRNA booster or who are immunized and had previous breakthrough Omicron infection. Additionally, both BQ and XBB are completely resistant to bebtelovimab, meaning there are now no clinically authorized therapeutic antibodies effective against these circulating variants. The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against BQ and XBB subvariants were lower by 13- to 81-fold and 66- to 155-fold, respectively, far beyond what had been observed to date. Monoclonal antibodies capable of neutralizing the original Omicron variant were largely inactive against these new subvariants, and the responsible individual spike mutations were identified. These subvariants were found to have similar ACE2-binding affinities as their predecessors. Together, our findings indicate that BQ and XBB subvariants present serious threats to current COVID-19 vaccines, render inactive all authorized antibodies, and may have gained dominance in the population because of their advantage in evading antibodies. [Display omitted] •BQ.1, BQ.1.1, XBB, and XBB.1 are the most resistant SARS-CoV-2 variants to date•Serum neutralization was markedly reduced, including with the bivalent booster•All clinical monoclonal antibodies were rendered inactive against these variants•The ACE2 affinity of these variants were similar to their parental strains Recent BQ and XBB subvariants of SARS-CoV-2 demonstrate dramatically increased ability to evade neutralizing antibodies, even those from people who received the bivalent mRNA booster or who are immunized and had previous breakthrough Omicron infection. Additionally, both BQ and XBB are completely resistant to bebtelovimab, meaning there are now no clinically authorized therapeutic antibodies effective against these circulating variants. The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against BQ and XBB subvariants were lower by 13- to 81-fold and 66- to 155-fold, respectively, far beyond what had been observed to date. Monoclonal antibodies capable of neutralizing the original Omicron variant were largely inactive against these new subvariants, and the responsible individual spike mutations were identified. These subvariants were found to have similar ACE2-binding affinities as their predecessors. Together, our findings indicate that BQ and XBB subvariants present serious threats to current COVID-19 vaccines, render inactive all authorized antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against BQ and XBB subvariants were lower by 13- to 81-fold and 66- to 155-fold, respectively, far beyond what had been observed to date. Monoclonal antibodies capable of neutralizing the original Omicron variant were largely inactive against these new subvariants, and the responsible individual spike mutations were identified. These subvariants were found to have similar ACE2-binding affinities as their predecessors. Together, our findings indicate that BQ and XBB subvariants present serious threats to current COVID-19 vaccines, render inactive all authorized antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.
Author	Yu, Jian Liu, Liyuan Liu, Lihong Li, Zhiteng Lauring, Adam S. Liu, Michael Guo, Yicheng Wang, Harris H. Huang, Yiming Sheng, Zizhang Gordon, Aubree Wang, Qian Iketani, Sho Bowen, Anthony D. Ho, David D. Wang, Maple Valdez, Riccardo
Author_xml	– sequence: 1 givenname: Qian surname: Wang fullname: Wang, Qian organization: Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA – sequence: 2 givenname: Sho surname: Iketani fullname: Iketani, Sho organization: Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA – sequence: 3 givenname: Zhiteng surname: Li fullname: Li, Zhiteng organization: Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA – sequence: 4 givenname: Liyuan surname: Liu fullname: Liu, Liyuan organization: Department of Systems Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA – sequence: 5 givenname: Yicheng surname: Guo fullname: Guo, Yicheng organization: Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA – sequence: 6 givenname: Yiming surname: Huang fullname: Huang, Yiming organization: Department of Systems Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA – sequence: 7 givenname: Anthony D. surname: Bowen fullname: Bowen, Anthony D. organization: Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA – sequence: 8 givenname: Michael surname: Liu fullname: Liu, Michael organization: Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA – sequence: 9 givenname: Maple surname: Wang fullname: Wang, Maple organization: Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA – sequence: 10 givenname: Jian surname: Yu fullname: Yu, Jian organization: Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA – sequence: 11 givenname: Riccardo surname: Valdez fullname: Valdez, Riccardo organization: Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA – sequence: 12 givenname: Adam S. surname: Lauring fullname: Lauring, Adam S. organization: Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA – sequence: 13 givenname: Zizhang surname: Sheng fullname: Sheng, Zizhang organization: Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA – sequence: 14 givenname: Harris H. surname: Wang fullname: Wang, Harris H. organization: Department of Systems Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA – sequence: 15 givenname: Aubree surname: Gordon fullname: Gordon, Aubree organization: Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA – sequence: 16 givenname: Lihong surname: Liu fullname: Liu, Lihong email: ll3411@cumc.columbia.edu organization: Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA – sequence: 17 givenname: David D. orcidid: 0000-0003-1627-149X surname: Ho fullname: Ho, David D. email: dh2994@cumc.columbia.edu organization: Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/36580913$$D View this record in MEDLINE/PubMed
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Keywords	COVID-19 receptor binding affinity SARS-CoV-2 neutralizing monoclonal antibody XBB antibody evasion XBB.1 BQ.1 BQ.1.1 mRNA vaccine
Language	English
License	This is an open access article under the CC BY license. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
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Snippet	The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional...
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SubjectTerms	antibodies Antibodies, Monoclonal Antibodies, Neutralizing Antibodies, Viral antibody evasion BQ.1 BQ.1.1 COVID-19 COVID-19 - immunology COVID-19 - virology COVID-19 infection COVID-19 Vaccines Humans Immune Evasion mRNA vaccine neutralization neutralizing monoclonal antibody receptor binding affinity SARS-CoV-2 SARS-CoV-2 - classification SARS-CoV-2 - genetics Severe acute respiratory syndrome coronavirus 2 vaccines XBB XBB.1
Title	Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants
URI	https://dx.doi.org/10.1016/j.cell.2022.12.018 https://www.ncbi.nlm.nih.gov/pubmed/36580913 https://www.proquest.com/docview/2759957966 https://www.proquest.com/docview/3153775938 https://pubmed.ncbi.nlm.nih.gov/PMC9747694
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