Why Avidity = great MABS15 Jun 2020 08:36
The paper describes how Scancell’s AvidiMab™ modifications to the constant region (Fc) of any
antibody can improve avidity, or strength of interaction, between the antibody and its target antigen,
thereby improving the antibody’s potential therapeutic properties. This same modification also has
demonstrated that Scancell’s own tumour-associated glycan (TaG) antibodies can directly kill tumour
cells.
affect macrophage function. For example, in a macaquemodel of SARS-CoV-1 infection, the presence of serumIgG antibodies to SARS-CoV-1 SP was associated withacute lung injury characterized by macrophag e activationand skewing of macrophages towards a pro-in?ammatory M1 phenotype.9This may contribute tothe pulmonary immunopathology demonstrated inmacaque models of SARS, which is characterized by tis-sue in?ltration by macrophages and neutrophils andincreased production of pro-in?ammatory cytokines andchemokines.10Similar mechanisms may also underliethe monocyte/macrophage dysfunction reported insevere COVID-19.1Additional evidence that SARS-CoV-1SP antibodies might drive pulmonary immunopathologyin SARS came from studies of mice immunized withSARS-CoV-1 vaccines, where production of SARS-CoV-1SP antibodies was associated with the occurrence of pul-monary immunopathology, characterized by a Th2response, following virus challenge.11If the amount of SARS-CoV-2 SP IgG antibody-enhancing activity, relative to neutralizing and other pro-tective antibody functions, is a determinant of COVID-19occurrence and severity, it will be important to determinethe underlying mechanisms as this might in?uence thedevelopment of not only human monoclonal antibodiesand convalescent plasma as therapies for COVID-19, butalso the selection of antigens for preventative vaccines. Ina study of SARS-CoV-1 infection in non-human primates,antibodies to different peptides of the SP exerted eitherneutralizing or enhancing activity,12suggesting that anti-gen characteristics are important. Antibody characteristicsmay also be important because SARS-CoV-1 infection ofa promonocyte cell line was enhanced by low concentra-tions of SARS-CoV-1 SP antibodies, whereas high anti-body concentrations resulted in virus neutralization.13However, as higher serum SARS-CoV-2 SP antibodylevels have been associated with worse clinical outcomesin COVID-19 patients,4other antibody characteristicsmay be more important. Clues to the nature of such anti-body characteristics might be provided by studies of den-gue virus infection, where low antibody neutralizationactivity correlated with low avidity of antigen binding toantibody Fab regions14while ADE correlated with analtered glycosylation pro?le of the Fc region of IgGantibodies, which enhanced binding of antibodies toFc?Rs on immu ne cells and the uptake of virus com-plexed with antibodies into those cells.15As both produc-tion of high avidity antibodies, which is dependent ongerminal centre function, and antibody glycosylation areadversely affected b
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