Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse®

Coughlin, Melissa; Lou, Gin; Martinez, Osvaldo; Masterman, Stephanie K.; Olsen, Ole A.; Moksa, Angelica A.; Farzan, Michael; Babcook, John S.; Prabhakar, Bellur S.

doi:10.1016/j.virol.2006.09.029

Cited by 70SARS-CoV-2 and COVID-19 ResearchMonoclonal and Polyclonal Antibodies ResearchAnimal Virus Infections Studies

Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse®

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Coughlin, Melissa, Lou, Gin, Martinez, Osvaldo, Masterman, Stephanie K., Olsen, Ole A., Moksa, Angelica A., Farzan, Michael, Babcook, John S. +1 more·2007·Virology

DOI 10.1016/j.virol.2006.09.029PMC PMC7103293

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Abstract

Passive therapy with neutralizing human monoclonal antibodies (mAbs) could be an effective therapy against severe acute respiratory syndrome coronavirus (SARS-CoV). Utilizing the human immunoglobulin transgenic mouse, XenoMouse, we produced fully human SARS-CoV spike (S) protein specific antibodies. Antibodies were examined for reactivity against a recombinant S1 protein, to which 200 antibodies reacted. Twenty-seven antibodies neutralized 200TCID(50) SARS-CoV (Urbani). Additionally, 57 neutralizing antibodies were found that are likely specific to S2. Mapping of the binding region was achieved with several S1 recombinant proteins. Most S1 reactive neutralizing mAbs bound to the RBD, aa 318-510. However, two S1 specific mAbs reacted with a domain upstream of the RBD between aa 12 and 261. Immunoglobulin gene sequence analyses suggested at least 8 different binding specificities. Unique human mAbs could be used as a cocktail that would simultaneously target several neutralizing epitopes and prevent emergence of escape mutants.

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Targeting the RBD has been a major focus in COVID-19 vaccine development.
“Eliciting an immune response that targets the RBD has been a major focus of vaccine development on the assumption that antibodies that bind this critical domain can prevent viral entry into host cells, thereby allowing for sterilizing immunity (that is, the complete prevention of infection)152–154, which would support herd immunity if vaccine coverage is sufficiently high155.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [154]

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Authors: Coughlin, M., Lou, G., Martinez, O., Masterman, S. K., Olsen, O. A., Moksa, A. A., Farzan, M., Babcook, J. S., & Prabhakar, B. S.
Affiliations: University of Illinois Chicago (US)
Brigham and Women's Hospital (US)
Corresponding author: Prabhakar, Bellur S.
ORCID: Coughlin, Melissa
Martinez, Osvaldo
Farzan, Michael
Prabhakar, Bellur S.
Venue: Virology
Publisher: Elsevier BV
Published: 2007-04
Volume: 361
Issue: 1
Pages: 93-102
ISSN: 0042-6822 (ISSN-L)
DOI: 10.1016/j.virol.2006.09.029
PMC: PMC7103293
OpenAlex: W2074326025
Cited by: 70
References: 37
Citations by year: 2022: 4 · 2021: 15 · 2020: 23 · 2019: 2 · 2017: 1 · 2016: 1 · 2014: 2 · 2013: 2 · 2012: 2
FWCI: 3.30
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2299 d)
Locations: Virology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
Keywords: SARS-CoV, neutralizing monoclonal antibodies, spike protein, S1 subunit, receptor binding domain, antibody specificity, passive immunotherapy, escape mutants, antibody cocktail
MeSH terms: Amino Acid Sequence, Animals, Antibodies, Monoclonal, Antibodies, Viral, Antibody Specificity, Hemagglutinins, Viral, Humans, Hybridomas, Immunoglobulins, Membrane Glycoproteins, Mice, Transgenic, Molecular Sequence Data, Neutralization Tests, Viral Envelope Proteins, Sequence Alignment, Severe Acute Respiratory Syndrome, Severe acute respiratory syndrome-related coronavirus, Mice, Spike Glycoprotein, Coronavirus

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Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse®

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