Broadly potent spike-specific human monoclonal antibodies inhibit SARS-CoV-2 Omicron sub-lineages
Open accessPublished version of a preprint
Abstract
Abstract The continuous emergence of SARS-CoV-2 variants of concern with mutated spike receptor binding domains has rendered many therapeutic mAbs ineffective. To date, there are no clinically authorized therapeutic antibodies effective against the predominant circulating sub-lineages BQ and XBB. Here, we report the isolation of broad and potent neutralizing HuMabs from a Danish healthcare worker infected with SARS-CoV-2 early in the pandemic. These HuMabs include a novel and genetically unique non-RBD-specific HuMab (K501SP6) which can neutralize Omicron sub-lineages BQ and XBB, and an RBD-specific HuMab (K501SP3) with high potency towards earlier circulating variants but was escaped by Omicron sub-lineages BA.5, BQ and XBB through F486 and E484 substitutions. Characterizing SARS-CoV-2 spike-specific HuMabs, including broadly reactive non-RBD-specific HuMabs, can give insight into the immune mechanisms involved in neutralization and immune evasion, which can be a valuable addition to already existing SARS-CoV-2 therapies.
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- Authors
- Walker, M. R., Underwood, A., Björnsson, K. H., Raghavan, S. S. R., Bassi, M. R., Binderup, A., Pham, L. V., Ramirez, S., Pinholt, M., Dagil, R., Knudsen, A. S., Idorn, M., Soegaard, M., Wang, K., Ward, A. B., Salanti, A., Bukh, J., & Barfod, L.
- Affiliations
- University of Copenhagen (DK)
- Scripps Research Institute (US)
- Hvidovre Hospital (DK)
- Aarhus University (DK)
- Corresponding author
- Barfod, Lea
- ORCID
- Venue
- Communications Biology
- Published
- 2024-10-02
- Volume
- 7
- Issue
- 1
- Pages
- 1239-1239
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC11445456
- OpenAlex
- W4403081168
- Cited by
- 6
- References
- 6
- Citations by year
- 2026: 4 · 2025: 2
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Communications Biology (publishedVersion, cc-by-nc-nd)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Novo Nordisk Fonden (NNF170C0026778)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- SARS-CoV-2, Omicron subvariants, BA.2.86, JN.1, human monoclonal antibodies, neutralizing antibodies, spike protein, receptor binding domain, immune evasion, antibody escape mutations, therapeutic antibodies
- MeSH terms
- COVID-19, SARS-CoV-2, Antibodies, Monoclonal, Antibodies, Viral, Epitopes, Humans, Neutralization Tests, Immune Evasion, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus
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