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

Animals Mice Antibodies, Neutralizing Antibodies, Viral COVID-19 / prevention & control Epitopes Ferritins / genetics Immunoglobulin Fc Fragments Mice, Transgenic SARS-CoV-2 / genetics Severe acute respiratory syndrome-related coronavirus Single-Domain Antibodies Spike Glycoprotein, Coronavirus / genetics Sharks

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
03 02 2023
Historique:
received: 18 10 2022
accepted: 13 01 2023
pubmed: 4 2 2023
medline: 8 2 2023
entrez: 3 2 2023
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-023-36106-x PMID: 36737435 PMC: PMC9896449
pubmed: 36737435
doi: 10.1038/s41467-023-36106-x
pii: 10.1038/s41467-023-36106-x
pmc: PMC9896449
doi:

Substances chimiques

Antibodies, Neutralizing 0
Antibodies, Viral 0
Epitopes 0
Ferritins 9007-73-2
Immunoglobulin Fc Fragments 0
Single-Domain Antibodies 0
Spike Glycoprotein, Coronavirus 0
spike protein, SARS-CoV-2 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

580

Subventions

Organisme : NIH HHS
ID : S10 OD021527
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM124165
Pays : United States

Informations de copyright

© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

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Auteurs

Wei-Hung Chen (WH)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
ORCID: 0000-0003-3724-9195

Agnes Hajduczki (A)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Elizabeth J Martinez (EJ)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
ORCID: 0000-0002-7755-7056

Hongjun Bai (H)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
ORCID: 0000-0002-3501-3974

Hanover Matz (H)

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
Institute of Marine and Environmental Technology, Baltimore, MD, USA.

Thomas M Hill (TM)

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
Institute of Marine and Environmental Technology, Baltimore, MD, USA.

Eric Lewitus (E)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

William C Chang (WC)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
ORCID: 0000-0003-4967-6426

Layla Dawit (L)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Caroline E Peterson (CE)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Phyllis A Rees (PA)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Adelola B Ajayi (AB)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Emily S Golub (ES)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Isabella Swafford (I)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
ORCID: 0000-0001-8638-2772

Vincent Dussupt (V)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
ORCID: 0000-0002-8579-6356

Sapna David (S)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Sandra V Mayer (SV)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Sandrine Soman (S)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Caitlin Kuklis (C)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
ORCID: 0000-0002-9974-6640

Courtney Corbitt (C)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Jocelyn King (J)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
ORCID: 0000-0003-3348-1632

Misook Choe (M)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Rajeshwer S Sankhala (RS)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Paul V Thomas (PV)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Michelle Zemil (M)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
ORCID: 0000-0002-1700-6658

Lindsay Wieczorek (L)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Tricia Hart (T)

Trudeau Institute, Saranac Lake, NY, USA.

Debora Duso (D)

Trudeau Institute, Saranac Lake, NY, USA.

Larry Kummer (L)

Trudeau Institute, Saranac Lake, NY, USA.

Lianying Yan (L)

Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.

Spencer L Sterling (SL)

Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.

Eric D Laing (ED)

Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.

Christopher C Broder (CC)

Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.
ORCID: 0000-0001-5382-0510

Jazmean K Williams (JK)

Integral Molecular, Philadelphia, PA, USA.

Edgar Davidson (E)

Integral Molecular, Philadelphia, PA, USA.

Benjamin J Doranz (BJ)

Integral Molecular, Philadelphia, PA, USA.
ORCID: 0000-0002-8245-3083

Shelly J Krebs (SJ)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
ORCID: 0000-0003-1136-1760

Victoria R Polonis (VR)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Dominic Paquin-Proulx (D)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
ORCID: 0000-0003-1407-3414

Morgane Rolland (M)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
ORCID: 0000-0003-3650-8490

William W Reiley (WW)

Trudeau Institute, Saranac Lake, NY, USA.

Gregory D Gromowski (GD)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
ORCID: 0000-0003-4576-4277

Kayvon Modjarrad (K)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Helen Dooley (H)

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA. hdooley@som.umaryland.edu.
Institute of Marine and Environmental Technology, Baltimore, MD, USA. hdooley@som.umaryland.edu.
ORCID: 0000-0002-2570-574X

M Gordon Joyce (MG)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA. gjoyce@eidresearch.org.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. gjoyce@eidresearch.org.
ORCID: 0000-0002-6808-7232

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Shark nanobodies with potent SARS-CoV-2...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Shark nanobodies with potent SARS-CoV-2...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps neutralisants › Shark nanobodies with potent SARS-CoV-2...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps antiviraux › Shark nanobodies with potent SARS-CoV-2...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › Shark nanobodies with potent SARS-CoV-2...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Épitopes › Shark nanobodies with potent SARS-CoV-2...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Métalloprotéines › Protéines de liaison au fer › Ferritines › Shark nanobodies with potent SARS-CoV-2...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Fragments d'immunoglobuline › Fragments Fc des immunoglobulines › Shark nanobodies with potent SARS-CoV-2...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Shark nanobodies with potent SARS-CoV-2...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › Shark nanobodies with potent SARS-CoV-2...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › Shark nanobodies with potent SARS-CoV-2...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Fragments d'immunoglobuline › Fragments Fab d'immunoglobuline › Anticorps à domaine unique › Shark nanobodies with potent SARS-CoV-2...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales structurales › Protéines de l'enveloppe virale › Protéines de fusion virale › Glycoprotéine de spicule des coronavirus › Shark nanobodies with potent SARS-CoV-2...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Poissons › Elasmobranchii › Requins › Shark nanobodies with potent SARS-CoV-2...