IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern

Matthew R. Chang, Luke Tomasovic, Natalia A. Kuzmina, Adam J. Ronk, Patrick O. Byrne, Rebecca Johnson, Nadia Storm, Eduardo Olmedillas, Yixuan J. Hou, Alexandra Schäfer, Sarah R. Leist, Longping V. Tse, Hanzhong Ke, Christian Coherd, Katrina Nguyen, Maliwan Kamkaew, Anna Honko, Quan Zhu, Galit Alter, Erica Ollmann SaphireJason S. McLellan, Anthony Griffiths, Ralph S. Baric, Alexander Bukreyev, Wayne A. Marasco

    Research output: Contribution to journalArticlepeer-review

    2 Scopus citations


    Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being employed to mitigate these challenges, but neutralization escape remains a major challenge and alternative strategies are needed. Here we present two anti-SARS-CoV-2 spike binding antibodies, one Class 1 and one Class 4, selected from our non-immune human single-chain variable fragment (scFv) phage library, that are engineered into four, fully-human IgG-like bispecific antibodies (BsAb). Prophylaxis of hACE2 mice and post-infection treatment of golden hamsters demonstrates the efficacy of the monospecific antibodies against the original Wuhan strain, while promising in vitro results with the BsAbs demonstrate enhanced binding and distinct synergistic effects on neutralizing activity against circulating variants of concern. In particular, one BsAb engineered in a tandem scFv-Fc configuration shows synergistic neutralization activity against several variants of concern including B.1.617.2. This work provides evidence that synergistic neutralization can be achieved using a BsAb scaffold, and serves as a foundation for the future development of broadly reactive BsAbs against emerging variants of concern.

    Original languageEnglish (US)
    Article number5814
    JournalNature communications
    Issue number1
    StatePublished - Dec 2022

    ASJC Scopus subject areas

    • Chemistry(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • General
    • Physics and Astronomy(all)


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