Reevaluation of antibody-dependent enhancement of infection in anti-SARS-CoV-2 therapeutic antibodies and mRNA-vaccine antisera using FcR- and ACE2-positive cells

Abstract

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.

Protective roles and protective mechanisms of neutralizing antibodies against SARS-CoV-2 infection and their potential clinical implications

“…This adverse condition may happen when a large number of antibodies with less potent neutralizing ability is administered and result in the deterioration of the disease condition or death. Similarly, another report observed ADE with sera from COVID-19 convalescents in an FcR- and ACE2-dependent manner ( 173 ). The FDA-approved mAb therapies, such as casirivimab, imdevimab, and sotrovimab, have been reported to cause ADE in FcR- and ACE2-positive cells ( 174 ).…”

The Novelty of mRNA Vaccines and Potential Harms: A Scoping Review

“…Furthermore, anti-spike IgG antibodies, as are produced by all of the mRNA vaccines, in addition to most other Covid-19 vaccines, are demonstrated to cause severe acute lung injury on re-exposure to the virus, suggesting a negative impact of a narrow immune response [71]. MERS-CoV vaccines have been tested in mice and rhesus macaques [72], revealing protection without visible histopathology Immune mediated danger from vaccines has been widely acknowledged to be an extant issue in the development of coronavirus vaccines [73][74][75][76][77][78][79], and is supported by current evidence [80]. During the rapid development of Covid-19 vaccines, it was an issue of concern that sufficient long-term monitoring for antibody-dependent enhancement (AD) effects be put into place [81,82].…”

“…Unfortunately, as of this writing, there is not data available on the long term impacts of Covid-19 vaccines, including effects resulting from rechallenge with the virus. Immune mediated danger from vaccines has been widely acknowledged to be an extant issue in the development of coronavirus vaccines [73][74][75][76][77][78][79], and is supported by current evidence [80]. During the rapid development of Covid-19 vaccines, it was an issue of concern that sufficient long-term monitoring for antibody-dependent enhancement (AD) effects be put into place [81,82].…”

The Novelty of mRNA Vaccines and Potential Harms: A Scoping Review

“…Unfortunately, as of this writing, there is not data available on the long term impacts of Covid-19 vaccines, including effects resulting from rechallenge with the virus. Immune mediated danger from vaccines has been widely acknowledged to be an extant issue in the development of coronavirus vaccines [106][107][108][109][110][111][112], and is supported by current evidence [113].…”

“…Immune mediated danger from vaccines has been widely acknowledged to be an extant issue in the development of coronavirus vaccines [106][107][108][109][110][111][112], and is supported by current evidence [113]. During the rapid development of Covid-19 vaccines, it was an issue of concern that sufficient long-term monitoring for antibody-dependent enhancement (ADE) effects be put into place [114,115].…”