Fast-Track Discovery of SARS-CoV-2-Neutralizing Antibodies from Human B Cells by Direct Functional Screening.

Publication date: Feb 22, 2024

As the COVID-19 pandemic revealed, rapid development of vaccines and therapeutic antibodies are crucial to guarantee a quick return to the status quo of society. In early 2020, we deployed our droplet microfluidic single-cell-based platform DROPZYLLA for the generation of cognate antibody repertoires of convalescent COVID-19 donors. Discovery of SARS-CoV-2-specific antibodies was performed upon display of antibodies on the surface of HEK293T cells by antigen-specific sorting using binding to the SARS-CoV-2 spike and absence of binding to huACE2 as the sort criteria. This efficiently yielded antibodies within 3-6 weeks, of which up to 100% were neutralizing. One of these, MTX-COVAB, displaying low picomolar neutralization IC50 of SARS-CoV-2 and with a neutralization potency on par with the Regeneron antibodies, was selected for GMP manufacturing and clinical development in June 2020. MTX-COVAB showed strong efficacy in vivo and neutralized all identified clinically relevant variants of SARS-CoV-2 at the time of its selection. MTX-COVAB completed GMP manufacturing by the end of 2020, but clinical development was stopped when the Omicron variant emerged, a variant that proved to be detrimental to all monoclonal antibodies already approved. The present study describes the capabilities of the DROPZYLLA platform to identify antibodies of high virus-neutralizing capacity rapidly and directly.

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Concepts Keywords
Dropzylla Antibodies, Neutralizing
Fast Antibodies, Neutralizing
June Antibodies, Viral
Vaccines Antibodies, Viral
antibody discovery
COVID-19
HEK293 Cells
Humans
monoclonal antibodies
neutralizing antibodies
Pandemics
SARS-CoV-2
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
viral variants

Semantics

Type Source Name
disease MESH COVID-19 pandemic
disease IDO cell
drug DRUGBANK Methotrexate
disease VO manufacturing
disease VO time
drug DRUGBANK Coenzyme M
disease MESH Infection
disease VO population
drug DRUGBANK Angiotensin II
disease IDO blood
disease IDO host
disease VO effectiveness
drug DRUGBANK Flunarizine
drug DRUGBANK Ilex paraguariensis leaf
disease VO Canada
disease VO USA
drug DRUGBANK Sodium lauryl sulfate
disease VO volume
disease IDO production
drug DRUGBANK Clostridium tetani toxoid antigen (formaldehyde inactivated)
disease VO protocol
disease VO manufacturer
disease VO gene
drug DRUGBANK L-Alanine
drug DRUGBANK Amino acids
drug DRUGBANK Polyethylene glycol
disease IDO assay
disease IDO infectivity
drug DRUGBANK Edetic Acid
drug DRUGBANK Methylcellulose
drug DRUGBANK Formaldehyde
drug DRUGBANK Gentian violet cation
disease VO injection
drug DRUGBANK L-Glutamine
drug DRUGBANK Dextrose unspecified form
disease VO dead
disease VO company
disease IDO replication
disease VO efficiency
disease MESH weight loss
disease VO dose
drug DRUGBANK Rituximab
drug DRUGBANK Aspartame
disease MESH virus infection
disease MESH point mutations
disease MESH infectious diseases
disease MESH emergency
disease IDO process
disease IDO immune response
disease VO vaccination
disease IDO intervention
disease MESH uncertainty
disease VO Advent
disease VO Imovax ID
disease VO viable
disease VO material combination
disease IDO facility
drug DRUGBANK Etodolac
disease MESH Pneumonia
drug DRUGBANK Guanosine
drug DRUGBANK (S)-Des-Me-Ampa
disease VO Glycoprotein
disease VO Betacoronavirus
disease MESH Breakthrough Infections

Original Article

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