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Chen, Wei-Hung; Hajduczki, Agnes; Martinez, Elizabeth J.; Bai, Hongjun; Matz, Hanover; Hill, Thomas M.; Lewitus, Eric; Chang, William C.; Dawit, Layla; Peterson, Caroline E.; Rees, Phyllis A.; Ajayi, Adelola B.; Golub, Emily S.; Swafford, Isabella; Dussupt, Vincent; David, Sapna; Mayer, Sandra V.; Soman, Sandrine; Kuklis, Caitlin; Corbitt, Courtney; King, Jocelyn; Choe, Misook; Sankhala, Rajeshwer S.; Thomas, Paul V.; [...]

Shark nanobodies with potent SARS-CoV-2 neutralizing activity and broad sarbecovirus reactivity

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  • Medientyp: E-Artikel
  • Titel: Shark nanobodies with potent SARS-CoV-2 neutralizing activity and broad sarbecovirus reactivity
  • Beteiligte: Chen, Wei-Hung; Hajduczki, Agnes; Martinez, Elizabeth J.; Bai, Hongjun; Matz, Hanover; Hill, Thomas M.; Lewitus, Eric; Chang, William C.; Dawit, Layla; Peterson, Caroline E.; Rees, Phyllis A.; Ajayi, Adelola B.; Golub, Emily S.; Swafford, Isabella; Dussupt, Vincent; David, Sapna; Mayer, Sandra V.; Soman, Sandrine; Kuklis, Caitlin; Corbitt, Courtney; King, Jocelyn; Choe, Misook; Sankhala, Rajeshwer S.; Thomas, Paul V.; [...]
  • Erschienen: Springer Science and Business Media LLC, 2023
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/s41467-023-36106-x
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Despite rapid and ongoing vaccine and therapeutic development, SARS-CoV-2 continues to evolve and evade, presenting a need for next-generation diverse therapeutic modalities. Here we show that nurse sharks immunized with SARS-CoV-2 recombinant receptor binding domain (RBD), RBD-ferritin (RFN), or spike protein ferritin nanoparticle (SpFN) immunogens elicit a set of new antigen receptor antibody (IgNAR) molecules that target two non-overlapping conserved epitopes on the spike RBD. Representative shark antibody variable NAR-Fc chimeras (ShAbs) targeting either of the two epitopes mediate cell-effector functions, with high affinity to all SARS-CoV-2 viral variants of concern, including the divergent Omicron strains. The ShAbs potently cross-neutralize SARS-CoV-2 WA-1, Alpha, Beta, Delta, Omicron BA.1 and BA.5, and SARS-CoV-1 pseudoviruses, and confer protection against SARS-CoV-2 challenge in the K18-hACE2 transgenic mouse model. Structural definition of the RBD-ShAb01-ShAb02 complex enabled design and production of multi-specific nanobodies with enhanced neutralization capacity, and picomolar affinity to divergent sarbecovirus clade 1a, 1b and 2 RBD molecules. These shark nanobodies represent potent immunotherapeutics both for current use, and future sarbecovirus pandemic preparation.</jats:p>
  • Zugangsstatus: Freier Zugang