Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants
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Abstract
SUMMARY The SARS-CoV-2 Omicron variant continues to evolve, with new BQ and XBB subvariants now rapidly expanding in Europe/US and Asia, respectively. As these new subvariants have additional spike mutations, they may possess altered antibody evasion properties. 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 who were boosted with a WA1/BA.5 bivalent mRNA vaccine. Compared to the ancestral strain D614G, serum neutralizing 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. A panel of monoclonal antibodies capable of neutralizing the original Omicron variant, including those with Emergency Use Authorization, were largely inactive against these new subvariants. The spike mutations that conferred antibody resistance were individually studied and structurally explained. Finally, the ACE2-binding affinities of the spike proteins of these novel subvariants were found to be similar to those of their predecessors. Taken together, our findings indicate that BQ and XBB subvariants present serious threats to the efficacy of current COVID-19 vaccines, render inactive all authorized monoclonal antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.
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Neutralization data suggests some of these new subvariants have even more immune escape than the original BA.5 subvariant.
“Neutralization data suggests some of these new subvariants have even more immune escape than the original BA.5 subvariant [43,44].”
From Assessing COVID-19 vaccine effectiveness against Omicron subvariants: Report from a meeting of the World Health Organization (2023) · cites this paper as [44]
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“…majority of the currently approved SARS-CoV-2 nAbs and cocktail therapy have been reported to reduce or abrogate neutralizing potency against emerging VOCs, especially for BQ.1.1 and XBB 13,14 . such as LY-CoV1404 15 , REGN10933 +REGN10987 16 , LY-CoV016+LY-CoV555 17,18 , and AZD1061+ AZD8895 19 .”
InfluentialSelf-citation
- Authors
- Wang, Q., Iketani, S., Li, Z., Liu, L., Guo, Y., Huang, Y., Bowen, A. D., Liu, M., Wang, M., Yu, J., Valdez, R., Lauring, A. S., Sheng, Z., Wang, H. H., Gordon, A., Liu, L., & Ho, D. D.
- Affiliations
- Aaron Diamond AIDS Research Center (US)
- Columbia University (US)
- University of Michigan (US)
- Corresponding author
- Liu, Lihong
- Ho, David D.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2023-01
- Volume
- 186
- Issue
- 2
- Pages
- 279-286.e8
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC9747694
- OpenAlex
- W4311359167
- Cited by
- 912
- References
- 45
- Citations by year
- 2026: 69 · 2025: 170 · 2024: 289 · 2023: 376 · 2022: 6
- FWCI
- 102.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ImmPort
- Funders
- NIH
- Janssen Pharmaceuticals
- Columbia University
- Bill & Melinda Gates Foundation
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2 Omicron subvariants, BQ.1, BQ.1.1, XBB, XBB.1, antibody escape, neutralizing antibodies, spike protein mutations, bivalent mRNA vaccine, monoclonal antibodies, ACE2 binding affinity
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, Antibodies, Monoclonal, Antibodies, Viral, Humans, Immune Evasion, Antibodies, Neutralizing
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