A hybrid approach involving a combination of conventional discovery and antibody repurposing to combat COVID-19.
By Dr. Priyom Bose, Ph.D.Aug 21 2023Reviewed by Benedette Cuffari, M.Sc. A recent Science Signaling study explores a hybrid approach, which involves a combination of conventional discovery and antibody repurposing, to combat severe acute respiratory syndrome coronavirus 2 infection, which is the causal agent of the coronavirus disease 2019 pandemic.
An antigen-specific B-cell sorting strategy is commonly used in the antibody discovery process. However, two major challenges in this approach include identifying high-quality peripheral blood mononuclear cells for antigen-specific B-cell sorting and determining lead therapeutic candidates. The therapeutic agent must have significant neutralization capacity and an easy large-scale development protocol.
About the study The current study explores a hybrid refocusing approach that combines repurposing techniques and conventional antibody discovery methods. The new method is focused on engineering the existing neutralizing antibody to target a related but resistant virus. Here, the SARS-CoV-1 nAb CR3022 was engineered to target SARS-CoV-2.
The library was in an environment that was free from unwanted mutations or mutations that would introduce N-linked glycan motifs. Each CDR loop library contained 100-200 unique coding variants. After effective sorting, antibody display vectors from the HC and LC libraries were harvested, and the region that encoded the HC and LC was amplified. A new HC and LC library was generated and subjected to a similar sorting phase to identify the best combination of mutations in the HCs and LCs.
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