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Antiviral Res . Neutralization or enhancement of SARS-CoV-2 infection by a monoclonal antibody targeting a specific epitope in the spike receptor-binding domain

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  • Antiviral Res . Neutralization or enhancement of SARS-CoV-2 infection by a monoclonal antibody targeting a specific epitope in the spike receptor-binding domain


    Antiviral Res


    . 2022 Mar 13;105290.
    doi: 10.1016/j.antiviral.2022.105290. Online ahead of print.
    Neutralization or enhancement of SARS-CoV-2 infection by a monoclonal antibody targeting a specific epitope in the spike receptor-binding domain


    Guan-Chun Lai 1 , Tai-Ling Chao 2 , Shiau-Yu Lin 1 , Han-Chieh Kao 3 , Ya-Min Tsai 3 , De-Chao Lu 1 , Yi-Wei Chiang 1 , Sui-Yuan Chang 4 , Shih-Chung Chang 5



    Affiliations

    Abstract

    Neutralizing antibodies (NAbs) are believed to be promising prophylactic and therapeutic treatment against the coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we reported two mouse monoclonal antibodies 7 Eb-4G and 1Ba-3H that specifically recognized the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein without exhibiting cross-reactivity with the S proteins of SARS-CoV and MERS-CoV. The binding epitopes of 7 Eb-4G and 1Ba-3H were respectively located in the regions of residues 457-476 and 477-496 in the S protein. Only 1Ba-3H exhibited the neutralizing activity for preventing the pseudotyped lentivirus from binding to the angiotensin-converting enzyme 2 (ACE2)-transfected HEK293T cells. The competitive ELISA further showed that 1Ba-3H interfered with the binding between RBD and ACE2. Epitope mapping experiments demonstrated that a single alanine replacement at residues 480, 482, 484, 485, and 488-491 in the RBD abrogated 1Ba-3H binding. 1Ba-3H exhibited the neutralizing activity against the wild-type, Alpha, Delta, and Epsilon variants of SARS-CoV-2, but lost the neutralizing activity against Gamma variant in the plaque reduction assay. On the contrary, 1Ba-3H enhanced the cellular infection of Gamma variant in a dose-dependent manner. Our findings suggest that the antibody-dependent enhancement of infection mediated by the RBD-specific antibody for different SARS-CoV-2 variants must be considered while developing the NAb.

    Keywords: ACE2; Antibody-dependent enhancement; COVID-19; Neutralizing antibody; SARS-CoV-2; Spike receptor binding domain.

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