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Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants

Author

Listed:
  • Anna R. Mäkelä

    (University of Helsinki)

  • Hasan Uğurlu

    (University of Helsinki)

  • Liina Hannula

    (University of Helsinki)

  • Ravi Kant

    (University of Helsinki
    University of Helsinki)

  • Petja Salminen

    (University of Helsinki)

  • Riku Fagerlund

    (University of Helsinki)

  • Sanna Mäki

    (University of Helsinki)

  • Anu Haveri

    (Finnish Institute for Health and Welfare)

  • Tomas Strandin

    (University of Helsinki)

  • Lauri Kareinen

    (University of Helsinki
    University of Helsinki)

  • Jussi Hepojoki

    (University of Helsinki)

  • Suvi Kuivanen

    (University of Helsinki)

  • Lev Levanov

    (University of Helsinki)

  • Arja Pasternack

    (University of Helsinki)

  • Rauno A. Naves

    (University of Helsinki)

  • Olli Ritvos

    (University of Helsinki)

  • Pamela Österlund

    (Finnish Institute for Health and Welfare)

  • Tarja Sironen

    (University of Helsinki
    University of Helsinki)

  • Olli Vapalahti

    (University of Helsinki
    University of Helsinki
    Helsinki University Hospital)

  • Anja Kipar

    (University of Helsinki
    University of Zurich)

  • Juha T. Huiskonen

    (University of Helsinki)

  • Ilona Rissanen

    (University of Helsinki)

  • Kalle Saksela

    (University of Helsinki
    Helsinki University Hospital)

Abstract

The emergence of increasingly immunoevasive SARS-CoV-2 variants emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Intranasal administration of neutralizing antibodies has shown encouraging protective potential but there remains a need for SARS-CoV-2 blocking agents that are less vulnerable to mutational viral variation and more economical to produce in large scale. Here we describe TriSb92, a highly manufacturable and stable trimeric antibody-mimetic sherpabody targeted against a conserved region of the viral spike glycoprotein. TriSb92 potently neutralizes SARS-CoV-2, including the latest Omicron variants like BF.7, XBB, and BQ.1.1. In female Balb/c mice intranasal administration of just 5 or 50 micrograms of TriSb92 as early as 8 h before but also 4 h after SARS-CoV-2 challenge can protect from infection. Cryo-EM and biochemical studies reveal triggering of a conformational shift in the spike trimer as the inhibitory mechanism of TriSb92. The potency and robust biochemical properties of TriSb92 together with its resistance against viral sequence evolution suggest that TriSb92 could be useful as a nasal spray for protecting susceptible individuals from SARS-CoV-2 infection.

Suggested Citation

  • Anna R. Mäkelä & Hasan Uğurlu & Liina Hannula & Ravi Kant & Petja Salminen & Riku Fagerlund & Sanna Mäki & Anu Haveri & Tomas Strandin & Lauri Kareinen & Jussi Hepojoki & Suvi Kuivanen & Lev Levanov &, 2023. "Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37290-6
    DOI: 10.1038/s41467-023-37290-6
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