IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern Article Swipe
Matthew Chang
,
Luke M. Tomasovic
,
Natalia A. Kuzmina
,
Adam J. Ronk
,
Patrick O. Byrne
,
Rebecca Johnson
,
Nadia Storm
,
Eduardo Olmedillas
,
Yixuan J. Hou
,
Alexandra Schäfer
,
Sarah R. Leist
,
Longping V. Tse
,
Hanzhong Ke
,
Christian D. Coherd
,
Katrina Nguyen
,
Maliwan Kamkaew
,
Anna N. Honko
,
Quan Zhu
,
Galit Alter
,
Erica Ollmann Saphire
,
Jason S. McLellan
,
Anthony Griffiths
,
Ralph S. Baric
,
Alexander Bukreyev
,
Wayne A. Marasco
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.17615/2rk6-ab97
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.17615/2rk6-ab97
Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being employed to mitigate these challenges, but neutralization escape remains a major challenge and alternative strategies are needed. Here we present two anti-SARS-CoV-2 spike binding antibodies, one Class 1 and one Class 4, selected from our non-immune human single-chain variable fragment (scFv) phage library, that are engineered into four, fully-human IgG-like bispecific antibodies (BsAb). Prophylaxis of hACE2 mice and post-infection treatment of golden hamsters demonstrates the efficacy of the monospecific antibodies against the original Wuhan strain, while promising in vitro results with the BsAbs demonstrate enhanced binding and distinct synergistic effects on neutralizing activity against circulating variants of concern. In particular, one BsAb engineered in a tandem scFv-Fc configuration shows synergistic neutralization activity against several variants of concern including B.1.617.2. This work provides evidence that synergistic neutralization can be achieved using a BsAb scaffold, and serves as a foundation for the future development of broadly reactive BsAbs against emerging variants of concern.
Related Topics
Concepts
Bispecific antibody
Neutralization
Antibody
Virology
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Coronavirus disease 2019 (COVID-19)
Chemistry
Immunology
Medicine
Monoclonal antibody
Infectious disease (medical specialty)
Internal medicine
Disease
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.17615/2rk6-ab97
- OA Status
- green
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4303627692
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4303627692Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.17615/2rk6-ab97Digital Object Identifier
- Title
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IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concernWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
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2022-10-08Full publication date if available
- Authors
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Matthew Chang, Luke M. Tomasovic, Natalia A. Kuzmina, Adam J. Ronk, Patrick O. Byrne, Rebecca Johnson, Nadia Storm, Eduardo Olmedillas, Yixuan J. Hou, Alexandra Schäfer, Sarah R. Leist, Longping V. Tse, Hanzhong Ke, Christian D. Coherd, Katrina Nguyen, Maliwan Kamkaew, Anna N. Honko, Quan Zhu, Galit Alter, Erica Ollmann Saphire, Jason S. McLellan, Anthony Griffiths, Ralph S. Baric, Alexander Bukreyev, Wayne A. MarascoList of authors in order
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https://doi.org/10.17615/2rk6-ab97Publisher landing page
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YesWhether a free full text is available
- OA status
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greenOpen access status per OpenAlex
- OA URL
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https://doi.org/10.17615/2rk6-ab97Direct OA link when available
- Concepts
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Bispecific antibody, Neutralization, Antibody, Virology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Coronavirus disease 2019 (COVID-19), Chemistry, Immunology, Medicine, Monoclonal antibody, Infectious disease (medical specialty), Internal medicine, DiseaseTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- Related works (count)
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10Other works algorithmically related by OpenAlex
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