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Shark nanobodies with potent SARS-CoV-2 neutralizing activity and broad sarbecovirus reactivity.
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; Zemil, Michelle; Wieczorek, Lindsay; Hart, Tricia; Duso, Debora; Kummer, Larry; Yan, Lianying; Sterling, Spencer L; Laing, Eric D; Broder, Christopher C; Williams, Jazmean K; Davidson, Edgar; Doranz, Benjamin J; Krebs, Shelly J; Polonis, Victoria R; Paquin-Proulx, Dominic; Rolland, Morgane; Reiley, William W; Gromowski, Gregory D; Modjarrad, Kayvon; Dooley, Helen; Joyce, M Gordon.
  • Chen WH; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Hajduczki A; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Martinez EJ; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Bai H; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Matz H; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Hill TM; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Lewitus E; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Chang WC; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Dawit L; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Peterson CE; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Rees PA; Institute of Marine and Environmental Technology, Baltimore, MD, USA.
  • Ajayi AB; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Golub ES; Institute of Marine and Environmental Technology, Baltimore, MD, USA.
  • Swafford I; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Dussupt V; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • David S; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Mayer SV; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Soman S; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Kuklis C; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Corbitt C; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • King J; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Choe M; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Sankhala RS; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Thomas PV; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Zemil M; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Wieczorek L; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Hart T; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Duso D; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Kummer L; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Yan L; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Sterling SL; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Laing ED; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Broder CC; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Williams JK; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Davidson E; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Doranz BJ; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Krebs SJ; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Polonis VR; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Paquin-Proulx D; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Rolland M; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Reiley WW; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Gromowski GD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Modjarrad K; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Dooley H; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Joyce MG; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
Nat Commun ; 14(1): 580, 2023 02 03.
Article in English | MEDLINE | ID: covidwho-2228819
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severe acute respiratory syndrome-related coronavirus / Single-Domain Antibodies / COVID-19 Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Animals Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2023 Document Type: Article Affiliation country: S41467-023-36106-x

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severe acute respiratory syndrome-related coronavirus / Single-Domain Antibodies / COVID-19 Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Animals Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2023 Document Type: Article Affiliation country: S41467-023-36106-x