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. 2023 Aug 30;12(9):1108.
doi: 10.3390/pathogens12091108.

In Vitro Antibody-Dependent Enhancement of SARS-CoV-2 Infection Could Be Abolished by Adding Human IgG

Xun Wang  1 , Minghui Li  1 , Panpan Lu  2 , Chen Li  1 , Chaoyue Zhao  1 , Xiaoyu Zhao  1 , Rui Qiao  1 , Yuchen Cui  1 , Yanjia Chen  1 , Jiayan Li  1 , Guonan Cai  1 , Pengfei Wang  1
Affiliations

In Vitro Antibody-Dependent Enhancement of SARS-CoV-2 Infection Could Be Abolished by Adding Human IgG

Xun Wang et al. Pathogens. .

Abstract

Evidence of antibody-dependent enhancement (ADE) of other viruses has raised concerns about the safety of SARS-CoV-2 vaccines and antibody therapeutics. In vitro studies have shown ADE of SARS-CoV-2 infection. In this study, we also found that vaccination/convalescent sera and some approved monoclonal antibodies can enhance SARS-CoV-2 infection of FcR-expressing B cells in vitro. However, the enhancement of SARS-CoV-2 infection can be prevented by blocking Fc-FcR interaction through the addition of human serum/IgG or the introduction of mutations in the Fc portion of the antibody. It should be noted that ADE activity observed on FcR-expressing cells in vitro may not necessarily reflect the situation in vivo; therefore, animal and clinical data should be included for ADE evaluation.

Keywords: COVID-19; SARS-CoV-2; antibody-dependent enhancement; convalescent serum; vaccination serum.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Polyclonal and monoclonal antibodies enhanced SARS-CoV-2 entry into FcR-expressing cells. (A) Neutralization of SARS-CoV-2 D614G pseudovirus by sera from seven vaccinated individuals and (B) seven convalescent individuals on Vero-E6 cells. (C) ADE of SARS-CoV-2 infection by sera from seven vaccinated individuals and (D) seven convalescent individuals on Raji cells. (E) Neutralization of SARS-CoV-2 D614G pseudovirus by mAbs on Vero-E6 cells. (F) ADE of SARS-CoV-2 infection by mAbs on Raji cells. Luciferase activity in the cell lysates was determined at 24 hpi. The experiment was performed in triplicate; means and standard deviations are shown.
Figure 2
Figure 2
In vitro ADE activities of SARS-CoV-2 neutralizing mAbs could be eliminated by adding human serum/IgG. ADE of SARS-CoV-2 pseudoviral infection on Raji cells mediated by (A) REGN10987 + REGN10933, (B) COV2-2130 + COV2-2196, (C) Brii-196, and (D) LY-CoV1404. Cells were cultured without or with human IgG (100 μg/mL), 5% or 10% NHS, and luciferase activity in the cell lysates was determined at 24 hpi. The experiment was performed in triplicate; means and standard deviations are shown.
Figure 3
Figure 3
In vitro ADE activities of SARS-CoV-2 mAbs could be abolished by modifying Fc region. ADE of SARS-CoV-2 D614G infection by (A) COV2-2130 + COV2-2196 and COV2-2130/LALA + COV2-2196/LALA, (B) LY-CoV1404 and LY-CoV1404/LALA, (C) LY-CoV1404 and LY-CoV1404/GASDALIE on Raji cells. (D) ADE of SARS-CoV-2 XBB.1.5 infection by LY-CoV1404 and LY-CoV1404/GASDALIE on Raji cells. Luciferase activity in the cell lysates was determined at 24 hpi. The experiment was performed in triplicate; means and standard deviations are shown.
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