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Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations.
Dussupt, Vincent; Sankhala, Rajeshwer S; Mendez-Rivera, Letzibeth; Townsley, Samantha M; Schmidt, Fabian; Wieczorek, Lindsay; Lal, Kerri G; Donofrio, Gina C; Tran, Ursula; Jackson, Nathaniel D; Zaky, Weam I; Zemil, Michelle; Tritsch, Sarah R; Chen, Wei-Hung; Martinez, Elizabeth J; Ahmed, Aslaa; Choe, Misook; Chang, William C; Hajduczki, Agnes; Jian, Ningbo; Peterson, Caroline E; Rees, Phyllis A; Rutkowska, Magdalena; Slike, Bonnie M; Selverian, Christopher N; Swafford, Isabella; Teng, I-Ting; Thomas, Paul V; Zhou, Tongqing; Smith, Clayton J; Currier, Jeffrey R; Kwong, Peter D; Rolland, Morgane; Davidson, Edgar; Doranz, Benjamin J; Mores, Christopher N; Hatziioannou, Theodora; Reiley, William W; Bieniasz, Paul D; Paquin-Proulx, Dominic; Gromowski, Gregory D; Polonis, Victoria R; Michael, Nelson L; Modjarrad, Kayvon; Joyce, M Gordon; Krebs, Shelly J.
  • Dussupt V; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Sankhala RS; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Mendez-Rivera L; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Townsley SM; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Schmidt F; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Wieczorek L; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Lal KG; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Donofrio GC; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Tran U; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Jackson ND; Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.
  • Zaky WI; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Zemil M; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Tritsch SR; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Chen WH; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Martinez EJ; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Ahmed A; U.S. Military HIV Research Program, 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.
  • Chang WC; U.S. Military HIV Research Program, 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.
  • Jian N; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Peterson CE; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Rees PA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Rutkowska M; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Slike BM; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Selverian CN; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Swafford I; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Teng IT; Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
  • Thomas PV; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Zhou T; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Smith CJ; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Currier JR; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Kwong PD; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Rolland M; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Davidson E; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Doranz BJ; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Mores CN; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Hatziioannou T; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Reiley WW; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Bieniasz PD; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Paquin-Proulx D; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Gromowski GD; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Polonis VR; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Michael NL; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Modjarrad K; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Joyce MG; Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.
  • Krebs SJ; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Nat Immunol ; 22(12): 1503-1514, 2021 12.
Article in English | MEDLINE | ID: covidwho-1493136
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 / Antibodies, Monoclonal Type of study: Prognostic study Topics: Variants Limits: Animals / Humans Language: English Journal: Nat Immunol Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: S41590-021-01068-z

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 / Antibodies, Monoclonal Type of study: Prognostic study Topics: Variants Limits: Animals / Humans Language: English Journal: Nat Immunol Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: S41590-021-01068-z