Adapting Neutralizing Antibodies to Viral Variants by Structure‐Guided Affinity Maturation Using Phage Display Technology Article Swipe
Frederik Peissert
,
Mattia Pedotti
,
Riccardo Corbellari
,
Luca Simonelli
,
Raoul De Gasparo
,
Elia Tamagnini
,
Louis Plüss
,
Abdullah Elsayed
,
Mattia Matasci
,
Roberto De Luca
,
Irene Cassaniti
,
Josè Camilla Sammartino
,
Antonio Piralla
,
Fausto Baldanti
,
Dario Neri
,
Luca Varani
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1002/gch2.202300088
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1002/gch2.202300088
Neutralizing monoclonal antibodies have achieved great efficacy and safety for the treatment of numerous infectious diseases. However, their neutralization potency is often rapidly lost when the target antigen mutates. Instead of isolating new antibodies each time a pathogen variant arises, it can be attractive to adapt existing antibodies, making them active against the new variant. Potential benefits of this approach include reduced development time, cost, and regulatory burden. Here a methodology is described to rapidly evolve neutralizing antibodies of proven activity, improving their function against new pathogen variants without losing efficacy against previous ones. The reported procedure is based on structure‐guided affinity maturation using combinatorial mutagenesis and phage display technology. Its use against the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is demonstrated, but it is suitable for any other pathogen. As proof of concept, the method is applied to CoV‐X2, a human bispecific antibody that binds with high affinity to the early SARS‐CoV‐2 variants but lost neutralization potency against Delta. Antibodies emerging from the affinity maturation selection exhibit significantly improved neutralization potency against Delta and no loss of efficacy against the other viral sequences tested. These results illustrate the potential application of structure‐guided affinity maturation in facilitating the rapid adaptation of neutralizing antibodies to pathogen variants.
Related Topics
Concepts
Neutralization
Phage display
Antibody
Potency
Affinity maturation
Monoclonal antibody
Virology
Pathogen
Neutralizing antibody
Biology
Mutagenesis
Peptide library
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Computational biology
Coronavirus disease 2019 (COVID-19)
Immunology
Mutant
In vitro
Peptide sequence
Medicine
Genetics
Gene
Infectious disease (medical specialty)
Pathology
Disease
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/gch2.202300088
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gch2.202300088
- OA Status
- gold
- Cited By
- 5
- References
- 53
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4386048606
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4386048606Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1002/gch2.202300088Digital Object Identifier
- Title
-
Adapting Neutralizing Antibodies to Viral Variants by Structure‐Guided Affinity Maturation Using Phage Display TechnologyWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-08-21Full publication date if available
- Authors
-
Frederik Peissert, Mattia Pedotti, Riccardo Corbellari, Luca Simonelli, Raoul De Gasparo, Elia Tamagnini, Louis Plüss, Abdullah Elsayed, Mattia Matasci, Roberto De Luca, Irene Cassaniti, Josè Camilla Sammartino, Antonio Piralla, Fausto Baldanti, Dario Neri, Luca VaraniList of authors in order
- Landing page
-
https://doi.org/10.1002/gch2.202300088Publisher landing page
- PDF URL
-
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gch2.202300088Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gch2.202300088Direct OA link when available
- Concepts
-
Neutralization, Phage display, Antibody, Potency, Affinity maturation, Monoclonal antibody, Virology, Pathogen, Neutralizing antibody, Biology, Mutagenesis, Peptide library, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Computational biology, Coronavirus disease 2019 (COVID-19), Immunology, Mutant, In vitro, Peptide sequence, Medicine, Genetics, Gene, Infectious disease (medical specialty), Pathology, DiseaseTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
5Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2, 2024: 2, 2023: 1Per-year citation counts (last 5 years)
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53Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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