Accelerated antibody discovery targeting the SARS-CoV-2 spike protein for COVID-19 therapeutic potential
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
Background
Rapid deployment of technologies capable of high-throughput and high-resolution screening is imperative for timely response to viral outbreaks. Risk mitigation in the form of leveraging multiple advanced technologies further increases the likelihood of identifying efficacious treatments in aggressive timelines.
Methods
In this study, we describe two parallel, yet distinct, in vivo approaches for accelerated discovery of antibodies targeting the severe acute respiratory syndrome coronavirus-2 spike protein. Working with human transgenic Alloy-GK mice, we detail a single B-cell discovery workflow to directly interrogate antibodies secreted from plasma cells for binding specificity and ACE2 receptor blocking activity. Additionally, we describe a concurrent accelerated hybridoma-based workflow utilizing a DiversimAb™ mouse model for increased diversity.
Results
The panel of antibodies isolated from both workflows revealed binding to distinct epitopes with both blocking and non-blocking profiles. Sequence analysis of the resulting lead candidates uncovered additional diversity with the opportunity for straightforward engineering and affinity maturation.
Conclusions
By combining in vivo models with advanced integration of screening and selection platforms, lead antibody candidates can be sequenced and fully characterized within one to three months.
Article activity feed
-
-
SciScore for 10.1101/2021.05.31.446421: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Mouse immunization, B-cell enrichment and hybridoma generation: Mouse immunizations were performed at Abveris (Canton, MA) in accordance with all IACUC protocols. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources ACE2 receptor blocking activity was interrogated by forming an antibody:S1 protein complex on the chip surface in a sequential format. antibody:S1suggested: NoneSoftware and Algorithms Sentences Resources Plasma cells exhibiting on-Beacon binding profiles of interest were exported for immunoglobulin sequence capture and analysis with the Geneious Biologics software. Geneiou…SciScore for 10.1101/2021.05.31.446421: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Mouse immunization, B-cell enrichment and hybridoma generation: Mouse immunizations were performed at Abveris (Canton, MA) in accordance with all IACUC protocols. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources ACE2 receptor blocking activity was interrogated by forming an antibody:S1 protein complex on the chip surface in a sequential format. antibody:S1suggested: NoneSoftware and Algorithms Sentences Resources Plasma cells exhibiting on-Beacon binding profiles of interest were exported for immunoglobulin sequence capture and analysis with the Geneious Biologics software. Geneious Biologicssuggested: (Geneious, RRID:SCR_010519)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
-
