Anti-SARS-CoV-2 monoclonal (RQ Bio)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Antibodies induced by SARS-CoV-2 infection or vaccination play pivotal roles in the body's defense against the virus; many monoclonal antibodies (mAbs) against SARS-CoV-2 have been cloned, and some neutralizing mAbs have been used as therapeutic drugs. In this study, we prepared an antibody panel consisting of 31 clones of anti-SARS-CoV-2 mAbs and analyzed and compared their biological activities. The mAbs used in this study were classified into different binding classes based on their binding epitopes and showed binding to the SARS-CoV-2 spike protein in different binding kinetics. A multiplex assay using the spike proteins of Alpha, Beta, Gamma, Delta, and Omicron variants clearly showed the different effects of variant mutations on the binding and neutralization activities of different binding classes of mAbs. In addition, we evaluated Fcγ receptor (FcγR) activation by immune complexes consisting of anti-SARS-CoV-2 mAb and SARS-CoV-2 pseudo-typed virus, and revealed differences in the FcγR activation properties among the binding classes of anti-SARS-CoV-2 mAbs. It has been reported that FcγR-mediated immune-cell activation by immune complexes is involved in the promotion of immunopathology of COVID-19; therefore, differences in the FcγR-activation properties of anti-SARS-CoV-2 mAbs are among the most important characteristics when considering the clinical impacts of anti-SARS-CoV-2 mAbs.

Several neutralizing mAbs directed against the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) have been developed and evaluated in clin. trials to prevent progression to severe disease in high-risk individuals.Starting in May 2021, we treated with i.v. (i.v.) mAbs 281 non-hospitalized patients, including eight patients with primary immunodeficiency and 31 with a secondary immunodeficiency, with mild-to-moderate COVID-19 at high risk of progression to severe disease and/or hospitalization: 134 females (F) and 144 males (M), with ages ranging from 22 to 90 years (mean, 71.4 years).Bamlanivimab/ etesevimab (700/1400 mg) was administered in 123 patients (56F;67 M), casirivimab/imdevimab (1200/1200 mg or 600/600 mg) in 86(44 F; 42 M) and sotrovimab (500 mg) in 72 (34 F; 38 M).In the treated population, 16 patients reported an adverse reaction to at least one drug and 14 had a pos. history of asthma.According to the grading system for generalized hypersensitivity reactions, clin. manifestations were classified as grade 1 (mild reaction), only urticarial rash, in two patients (one bamlanivimab/etesevimab and one sotrovimab), and grade 2 (moderate reaction), urticarial rash associated with rhinorrhea, eye itching, throat tightness, and mild dyspnea in the third patient (bamlanivimab/etesevimab).No severe hypersensitivity reactions (grades 3 and 4), including hypoxia, hypotension, or neurol. compromise, occurred.None of the three patients had allergy and/or anaphylaxis history.Our data confirm the low incidence of IHRs during i.v. infusion of anti-SARS-CoV-2 mAbs observed in clin. trials.The main strength of our experience is that anamnestic data collection, mAbs administration, and IHRs evaluation have been managed by an allergist-immunologist expert in recognizing signs or symptoms of hypersensitivity reactions.One limitation of this study is that we did not perform any confirmatory test at that time because of the COVID-19 pandemic that affected our ability to make the necessary investigations and we are now conducting these investigations