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Hexamerization of Anti-SARS CoV IgG1 Antibodies Improves Neutralization Capacity.
Pande, Kalyan; Hollingsworth, Scott A; Sam, Miranda; Gao, Qinshan; Singh, Sujata; Saha, Anasuya; Vroom, Karin; Ma, Xiaohong Shirley; Brazell, Tres; Gorman, Dan; Chen, Shi-Juan; Raoufi, Fahimeh; Bailly, Marc; Grandy, David; Sathiyamoorthy, Karthik; Zhang, Lan; Thompson, Rob; Cheng, Alan C; Fayadat-Dilman, Laurence; Geierstanger, Bernhard H; Kingsley, Laura J.
  • Pande K; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
  • Hollingsworth SA; Discovery Chemistry, Merck & Co., Inc., South San Francisco, CA, United States.
  • Sam M; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
  • Gao Q; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
  • Singh S; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
  • Saha A; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
  • Vroom K; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
  • Ma XS; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
  • Brazell T; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
  • Gorman D; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
  • Chen SJ; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
  • Raoufi F; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
  • Bailly M; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
  • Grandy D; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
  • Sathiyamoorthy K; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
  • Zhang L; Infectious Disease and Vaccine Discovery, Merck & Co., Inc., West Point, PA, United States.
  • Thompson R; Discovery Chemistry, Merck & Co., Inc., South San Francisco, CA, United States.
  • Cheng AC; Discovery Chemistry, Merck & Co., Inc., South San Francisco, CA, United States.
  • Fayadat-Dilman L; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
  • Geierstanger BH; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
  • Kingsley LJ; Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States.
Front Immunol ; 13: 864775, 2022.
Article in English | MEDLINE | ID: covidwho-1862607
ABSTRACT
The SARS-CoV-2 pandemic and particularly the emerging variants have deepened the need for widely available therapeutic options. We have demonstrated that hexamer-enhancing mutations in the Fc region of anti-SARS-CoV IgG antibodies lead to a noticeable improvement in IC50 in both pseudo and live virus neutralization assay compared to parental molecules. We also show that hexamer-enhancing mutants improve C1q binding to target surface. To our knowledge, this is the first time this format has been explored for application in viral neutralization and the studies provide proof-of-concept for the use of hexamer-enhanced IgG1 molecules as potential anti-viral therapeutics.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Diagnostic study Topics: Variants Limits: Humans Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.864775

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Diagnostic study Topics: Variants Limits: Humans Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.864775