An antibody-dependent enhancement (ADE) activity eliminated neutralizing antibody with potent prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus monkeys

Abstract

Efficacious interventions are urgently needed for the treatment of COVID-19. Here, we report a monoclonal antibody (mAb), MW05, showing high SARS-CoV-2 neutralizing activity by disrupting the interaction of receptor binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2) receptor. Crosslinking of Fc with FcγRIIB mediates antibody-dependent enhancement (ADE) activity by MW05. This activity was eliminated by introducing the LALA mutation to the Fc region (MW05/LALA). Most importantly, potent prophylactic and therapeutic effects against SARS-CoV-2 were observed in rhesus monkeys. A single dose of MW05/LALA completely blocked the infection of SARS-CoV-2 in a study of its prophylactic effect and totally cleared SARS-CoV-2 in three days in a treatment setting. These results pave the way for the development of MW05/LALA as an effective strategy for combating COVID-19.

REGN-COV2 antibody cocktail prevents and treats SARS-CoV-2 infection in rhesus macaques and hamsters

“…Potential for antibody mediated enhancement of disease (ADE) is a serious concern for antibody-based therapeutics and vaccines. And although a recent report showed ability of some anti-spike mAbs to mediate pseudovirus entry into FcγR expressing cell lines, these data do not address whether similar behavior would be observed with authentic SARS-CoV-2 virus and primary immune cells (Wang S. et al, 2020). Our results are consistent with no evidence of enhanced disease in clinical studies assessing convalescent plasma therapy (Li et al, 2020).…”

An updated overview of recent advances, challenges, and clinical considerations of IL-6 signaling blockade in severe coronavirus disease 2019 (COVID-19)

“…Serum therapy was used in the H1N1 influenza pandemic in 2009. Whereas lots of cytokines are released to the bloodstream in the COVID-19 cytokine storm, using multiple and consecutive drugs could be more tolerated by therapeutic plasma exchange (TPE) [190] , [191] , [192] . TPE is used for eliminating plasma antibodies, toxins, and abnormal proteins that have been produced due to COVID-19.…”

Evaluation of strategies to modify Anti-SARS-CoV-2 monoclonal antibodies for optimal functionality as therapeutics

“…Unlike traditional infection of cells, this infection occurs in the absence of the known cellular receptor for virus entry and is dependent on the expression of FcγRs on the surface of the target cell, traditionally FCGR-2A 2A for SARS CoV1 and MERS [ 23 ], and the presence of antibodies targeting the virus. Importantly, recent evidence suggests that some SARS CoV2–specific antibodies, including both monoclonal antibodies [ 62 , 63 ] and polyclonal serum from convalescent subjects [ 63 ], can also mediate this effect, albeit in an FcγR 2B-dependent manner. To determine if this panel of monoclonal antibodies could induce a similar effect, the full antibody panel was tested for their ability to drive the infection of ACE2-negative but FCGR-2A-positive Raji cells.…”