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Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Hyperimmune Immunoglobulin Demonstrates Potent Neutralization and Antibody-Dependent Cellular Cytotoxicity and Phagocytosis Through N and S Proteins.
Díez, José María; Romero, Carolina; Cruz, María; Vandeberg, Peter; Merritt, William Keither; Pradenas, Edwards; Trinité, Benjamin; Blanco, Julià; Clotet, Bonaventura; Willis, Todd; Gajardo, Rodrigo.
  • Díez JM; Bioscience Research and Development, Scientific Innovation Office, Grifols, Barcelona, Spain.
  • Romero C; Bioscience Research and Development, Scientific Innovation Office, Grifols, Barcelona, Spain.
  • Cruz M; Bioscience Research and Development, Scientific Innovation Office, Grifols, Barcelona, Spain.
  • Vandeberg P; Bioscience Research and Development, Scientific Innovation Office, Grifols, Barcelona, Spain.
  • Merritt WK; Bioscience Research and Development, Scientific Innovation Office, Grifols, Barcelona, Spain.
  • Pradenas E; IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Badalona, Catalonia, Spain.
  • Trinité B; IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Badalona, Catalonia, Spain.
  • Blanco J; IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Badalona, Catalonia, Spain.
  • Clotet B; University of Vic-Central University of Catalonia (UVic-UCC), Vic, Catalonia, Spain.
  • Willis T; IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Badalona, Catalonia, Spain.
  • Gajardo R; University of Vic-Central University of Catalonia (UVic-UCC), Vic, Catalonia, Spain.
J Infect Dis ; 225(6): 938-946, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1740891
ABSTRACT

BACKGROUND:

Although coronavirus disease 2019 (COVID-19) vaccinations have provided a significant reduction in infections, effective COVID-19 treatments remain an urgent need.

METHODS:

Functional characterization of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hyperimmune immunoglobulin (hIG) from human convalescent plasma was performed by different virus neutralization methodologies (plaque reduction, virus-induced cytotoxicity, median tissue culture infectious dose [TCID50] reduction, and immunofluorimetry) at different laboratories using geographically different SARS-CoV-2 isolates (USA [1], Italy [1], and Spain [2]; 2 containing the D614G mutation). Neutralization capacity against the original Wuhan SARS-CoV-2 strain and variants (D614G mutant, B.1.1.7, P.1, and B.1.351) was evaluated using a pseudovirus expressing the corresponding spike (S) protein. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) was also evaluated.

RESULTS:

All SARS-CoV-2 isolates were potently neutralized by hIG as shown by all 4 methodologies. Wild-type SARS-CoV-2 and variants were effectively neutralized using the pseudovirus. The hIG (IgG type) induced ADCC and ADCP against SARS-CoV-2 N and S proteins but not E protein. Very low concentrations (25-100 µg IgG/mL) were required. A potent effect was triggered by antibodies in hIG solutions against the SARS-CoV-2 S and N proteins.

CONCLUSIONS:

Beyond neutralization, IgG Fc-dependent pathways may play a role in combatting SARS-CoV-2 infections using COVID-19 hIG. This could be especially relevant for the treatment of more neutralization-resistant SARS-CoV-2 variants.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Phagocytosis / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 / Antibodies, Viral / Antibody-Dependent Cell Cytotoxicity Type of study: Experimental Studies Topics: Vaccines / Variants Limits: Humans Language: English Journal: J Infect Dis Year: 2022 Document Type: Article Affiliation country: Infdis

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Phagocytosis / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 / Antibodies, Viral / Antibody-Dependent Cell Cytotoxicity Type of study: Experimental Studies Topics: Vaccines / Variants Limits: Humans Language: English Journal: J Infect Dis Year: 2022 Document Type: Article Affiliation country: Infdis