Reevaluation of antibody-dependent enhancement of infection in anti-SARS-CoV-2 therapeutic antibodies and mRNA-vaccine antisera using FcR- and ACE2-positive cells
Shimizu et al.,
Reevaluation of antibody-dependent enhancement of infection in anti-SARS-CoV-2 therapeutic antibodies and..,
Scientific Reports, doi:10.1038/s41598-022-19993-w
In Vitro study showing that casirivimab/imdevimab may induce antibody-dependent enhancement (ADE) within a specific concentration range. No ADE was observed for sotrovimab.
Shimizu et al., 16 Sep 2022, Japan, peer-reviewed, 12 authors.
Contact:
kmiyazaki@micantechnologies.com, shioda@biken.osaka-u.ac.jp.
Abstract: www.nature.com/scientificreports
OPEN
Reevaluation
of antibody‑dependent
enhancement of infection
in anti‑SARS‑CoV‑2 therapeutic
antibodies and mRNA‑vaccine
antisera using FcR‑
and ACE2‑positive cells
Jun Shimizu1, Tadahiro Sasaki2, Ritsuko Koketsu2, Ryo Morita3, Yuka Yoshimura1,
Ami Murakami1, Yua Saito1, Toshie Kusunoki1, Yoshihiro Samune2, Emi E. Nakayama2,
Kazuo Miyazaki1* & Tatsuo Shioda2*
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 mRNAvaccinated 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.
Therapeutic Ab drugs targeting SARS-CoV-2 S-protein have shown high preventive efficacy against disease
development1–3. In addition, current SARS-CoV-2 mRNA vaccines for humans also target the S-protein on
viruses as a critical a ntigen4. These mRNA vaccines generate robust neutralizing A
bs5–7, but for both Ab drugs
and vaccines targeting the S-protein, the possible induction of Ab-dependent enhancement (ADE) of infection
is a concern8–11. Recent reports have demonstrated that neutralizing mAbs against S-protein can exhibit ADE
activity in a limited window of Ab c oncentrations12–14. An important issue requiring reconsideration is that the
cells used to evaluate ADE potential are different in each report. In many cases, Fc-receptor (FcR)-positive and
angiotensin-converting enzyme 2 (ACE2, the major receptor for SARS-CoV-215–17)-negative cells lines (Raji,
THP-1, and K562) are used as host cells for infection of SARS-CoV-2 pseudo-viruses expressing S-protein
or authentic SARS-CoV-212–14,18,19. These reports have demonstrated that some anti-S protein mAbs have the
potential to induce ADE of infection. The observed ADE can be blocked in the presence of FcR-blocker, demonstrating FcR dependence. Likewise, the Ab drugs casirivimab and imdevimab1,20,21, which target the SARSCoV-2 S-protein, have also been evaluated by using FcR-positive and ACE2-negative cell lines (U937, THP-1,
1
MiCAN Technologies Inc, KKVP 1‑36, Goryo‑ohara, Nishikyo‑Ku, Kyoto 615‑8245, Japan. 2Department of Viral
Infections, Research Institute for Microbial Diseases, Osaka University, 3‑1, Yamada‑oka, Suita, Osaka 565‑0871,
Japan. 3Osaka City Juso Hospital, 2‑12‑27, Nonakakita, Yodogawa‑ku, Osaka 532‑0034, Japan. *email:
kmiyazaki@micantechnologies.com; shioda@biken.osaka-u.ac.jp
Scientific Reports |
(2022) 12:15612
|..
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