Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations.

Amino Acid Sequence Animals Antibodies, Monoclonal / administration & dosage Antibodies, Neutralizing / chemistry Antibodies, Viral / immunology Binding Sites / genetics COVID-19 / immunology Disease Models, Animal Dose-Response Relationship, Drug Epitope Mapping Epitopes / chemistry Humans Mice, Transgenic Neutralization Tests Protein Binding Protein Conformation SARS-CoV-2 / genetics Sequence Homology, Amino Acid Spike Glycoprotein, Coronavirus / genetics Survival Analysis

Journal

Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354

Informations de publication

Date de publication:
12 2021
Historique:
received: 16 06 2021
accepted: 08 10 2021
pubmed: 31 10 2021
medline: 21 12 2021
entrez: 30 10 2021
Statut: ppublish

Résumé

Prevention of viral escape and increased coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern require therapeutic monoclonal antibodies (mAbs) targeting multiple sites of vulnerability on the coronavirus spike glycoprotein. Here we identify several potent neutralizing antibodies directed against either the N-terminal domain (NTD) or the receptor-binding domain (RBD) of the spike protein. Administered in combinations, these mAbs provided low-dose protection against SARS-CoV-2 infection in the K18-human angiotensin-converting enzyme 2 mouse model, using both neutralization and Fc effector antibody functions. The RBD mAb WRAIR-2125, which targets residue F486 through a unique heavy-chain and light-chain pairing, demonstrated potent neutralizing activity against all major SARS-CoV-2 variants of concern. In combination with NTD and other RBD mAbs, WRAIR-2125 also prevented viral escape. These data demonstrate that NTD/RBD mAb combinations confer potent protection, likely leveraging complementary mechanisms of viral inactivation and clearance.

Identifiants

DOI: 10.1038/s41590-021-01068-z PMID: 34716452 PMC: PMC8642242
pubmed: 34716452
doi: 10.1038/s41590-021-01068-z
pii: 10.1038/s41590-021-01068-z
pmc: PMC8642242
doi:

Substances chimiques

Antibodies, Monoclonal 0
Antibodies, Neutralizing 0
Antibodies, Viral 0
Epitopes 0
Spike Glycoprotein, Coronavirus 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1503-1514

Subventions

Organisme : NIH HHS
ID : S10 OD021527
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93019C00073
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI078788
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI050111
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM124165
Pays : United States

Informations de copyright

© 2021. The Author(s).

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Auteurs

Vincent Dussupt (V)

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

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.

Letzibeth Mendez-Rivera (L)

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

Samantha M Townsley (SM)

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

Fabian Schmidt (F)

Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.

Lindsay Wieczorek (L)

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

Kerri G Lal (KG)

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

Gina C Donofrio (GC)

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

Ursula Tran (U)

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

Nathaniel D Jackson (ND)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
ORCID: 0000-0002-9654-6926

Weam I Zaky (WI)

U.S. Military HIV Research Program, 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.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
ORCID: 0000-0002-1700-6658

Sarah R Tritsch (SR)

Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.

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.

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.

Aslaa Ahmed (A)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
ORCID: 0000-0003-3093-4982

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.

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

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.

Ningbo Jian (N)

U.S. Military HIV Research Program, 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.

Magdalena Rutkowska (M)

Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.

Bonnie M Slike (BM)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
ORCID: 0000-0003-4132-4637

Christopher N Selverian (CN)

Integral Molecular, Philadelphia, PA, USA.
ORCID: 0000-0002-1047-4336

Isabella Swafford (I)

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

I-Ting Teng (IT)

Vaccine Research Center, NIAID, NIH, 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.

Tongqing Zhou (T)

Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA.
ORCID: 0000-0002-3935-4637

Clayton J Smith (CJ)

NCI, NIH, Bethesda, MD, USA.

Jeffrey R Currier (JR)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
ORCID: 0000-0002-5696-0268

Peter D Kwong (PD)

Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA.
ORCID: 0000-0003-3560-232X

Morgane Rolland (M)

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

Edgar Davidson (E)

Integral Molecular, Philadelphia, PA, USA.

Benjamin J Doranz (BJ)

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

Christopher N Mores (CN)

Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
ORCID: 0000-0001-6678-9049

Theodora Hatziioannou (T)

Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.

William W Reiley (WW)

Trudeau Institute, Saranac Lake, NY, USA.

Paul D Bieniasz (PD)

Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.
Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA.
ORCID: 0000-0002-2368-3719

Dominic Paquin-Proulx (D)

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

Gregory D Gromowski (GD)

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

Victoria R Polonis (VR)

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

Nelson L Michael (NL)

Center of Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
ORCID: 0000-0001-5882-5548

Kayvon Modjarrad (K)

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

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

Shelly J Krebs (SJ)

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

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Classifications MeSH

questionsmedicales.fr › Sciences de l'information › Sources d'information › Services d'information › Documentation › Données de séquences moléculaires › Séquence d'acides aminés › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Eucaryotes › Animaux › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps neutralisants › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps antiviraux › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Sites de fixation › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes toxicologiques › Relation dose-effet des médicaments › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Techniques d'investigation › Techniques de sonde moléculaire › Cartographie d'interactions entre protéines › Cartographie épitopique › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Épitopes › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Tests immunologiques › Tests sérologiques › Tests de neutralisation › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Phénomènes génétiques › Similitude de séquences › Similitude de séquences d'acides aminés › Low-dose in vivo protection and neutralization...
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 › Low-dose in vivo protection and neutralization...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de survie › Low-dose in vivo protection and neutralization...