Shimizu et al.: "Reevaluation of antibody-dependent enhancement of infection in anti-SARS-CoV-2 therapeutic antibodies and mRNA-vaccine antisera using FcR- and ACE2-positive cells
we demonstrate (in-vitro) that certain monoclonal Abs (mAbs) approved as therapeutic neutralizing anti-S-protein mAbs for human usage have potential to cause ADE in a narrow range of Ab concentration.
ADE emerges via Moderna mRNA injection, in-vitro. Researchers report “we investigated sera from mRNA (Moderna)-vaccinated individuals in terms of ADE-causing potential by using the same double-positive cells. Here, we show that the casirivimab and imdevimab mAbs have the ability to induce ADE, but sotrovimab does not.”
‘Many therapeutic antibodies (Abs) and mRNA vaccines, both targeting SARS-CoV-2 spike protein (S-protein), have been developed and approved in order to combat the ongoing COVID-19 pandemic. In consideration of these developments, a common concern has been the potential for Ab-dependent enhancement (ADE) of infection caused by inoculated or induced Abs. Although the preventive and therapeutic effects of these Abs are obvious, little attention has been paid to the influence of the remaining and dwindling anti-S-protein Abs in vivo.
Here, we demonstrate that certain monoclonal Abs (mAbs) approved as therapeutic neutralizing anti-S-protein mAbs for human usage have the potential to cause ADE in a narrow range of Ab concentrations. Although sera collected from mRNA-vaccinated individuals exhibited neutralizing activity, some sera gradually exhibited dominance of ADE activity in a time-dependent manner. None of the sera examined exhibited neutralizing activity against infection with the Omicron strain. Rather, some ADE of Omicron infection was observed in some sera. These results suggest the possible emergence of adverse effects caused by these Abs in addition to the therapeutic or preventive effect.’
Note this is in-vitro and hard objective patient-important outcomes are not studied. Yet quite instructive. Figure 1 A below really is the key graph for it reveals a point in antibody concentration (x-axis) where the viral replication is surged. So there seems to be an optimal concentration of antibodies (they looked at casirivimab and imdevimab and sotrovimab) at which point ADE plays out (increased viral replication). Seems that at a certain concentration, antibodies or no antibodies is the same. At a certain higher concentration of antibodies, then there is the potential as we see here, for mitigation of viral replication (Y-axis) (Figure 1 A).
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