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Cell Rep . Deciphering a reliable synergistic bispecific strategy of rescuing antibodies for SARS-CoV-2 escape variants, including BA.2.86, EG.5.1, and JN.1

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  • Cell Rep . Deciphering a reliable synergistic bispecific strategy of rescuing antibodies for SARS-CoV-2 escape variants, including BA.2.86, EG.5.1, and JN.1

    Cell Rep


    . 2024 Jun 7;43(6):114338.
    doi: 10.1016/j.celrep.2024.114338. Online ahead of print. Deciphering a reliable synergistic bispecific strategy of rescuing antibodies for SARS-CoV-2 escape variants, including BA.2.86, EG.5.1, and JN.1

    Zhou Tong 1 , Jianyu Tong 2 , Wenwen Lei 3 , Yufeng Xie 4 , Yingzi Cui 4 , Guowen Jia 5 , Shihua Li 4 , Zezhong Zhang 4 , Zhimin Cheng 2 , Xiao Xing 2 , Haiyun Ma 5 , Lan Deng 6 , Rong Zhang 4 , Xin Zhao 4 , Kefang Liu 4 , Qihui Wang 4 , Jianxun Qi 4 , Haomin Huang 6 , Rui Song 7 , Zhaoming Su 5 , Guizhen Wu 3 , Jing Lou 8 , George Fu Gao 9



    AffiliationsFree article Abstract

    The game between therapeutic monoclonal antibodies (mAbs) and continuously emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has favored the virus, as most therapeutic mAbs have been evaded. Addressing this challenge, we systematically explored a reproducible bispecific antibody (bsAb)-dependent synergistic effect in this study. It could effectively restore the neutralizing activity of the bsAb when any of its single mAbs is escaped by variants. This synergy is primarily attributed to the binding angle of receptor-binding domain (RBD)-5, facilitating inter-spike cross-linking and promoting cryptic epitope exposure that classical antibody cocktails cannot achieve. Furthermore, RBD-5 with RBD-2, RBD-6, and RBD-7, alongside RBD-8, also exhibit significantly enhanced effects. This study not only shifts the paradigm in understanding antibody interactions but paves the way for developing more effective therapeutic antibodies against rapidly mutating SARS-CoV-2, with Dia-19 already showing promise against emerging variants like BA.2.86, EG.5.1, and JN.1.

    Keywords: CP: Immunology; SARS-CoV-2; cryptic epitopes; non-RBM; phage display; scDb; single-chain diabody; synergistic effect.

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