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A multispecific antibody prevents immune escape and confers pan-SARS-CoV-2 neutralization.
Misasi, John; Wei, Ronnie R; Wang, Lingshu; Pegu, Amarendra; Wei, Chih-Jen; Oloniniyi, Olamide K; Zhou, Tongqing; Moliva, Juan I; Zhao, Bingchun; Choe, Misook; Yang, Eun Sung; Zhang, Yi; Boruszczak, Marika; Chen, Man; Leung, Kwan; Li, Juan; Yang, Zhi-Yong; Andersen, Hanne; Carlton, Kevin; Godbole, Sucheta; Harris, Darcy R; Henry, Amy R; Ivleva, Vera B; Lei, Paula; Liu, Cuiping; Longobardi, Lindsay; Merriam, Jonah S; Nase, Danielle; Olia, Adam S; Pessaint, Laurent; Porto, Maciel; Shi, Wei; Wolff, Jeremy J; Douek, Daniel C; Suthar, Mehul S; Gall, Jason; Koup, Richard A; Kwong, Peter D; Mascola, John R; Nabel, Gary J; Sullivan, Nancy J.
Afiliación
  • Misasi J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Wei RR; Modex Therapeutics Inc., an OPKO Health Company, Natick, MA 01760, USA.
  • Wang L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Pegu A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Wei CJ; Modex Therapeutics Inc., an OPKO Health Company, Natick, MA 01760, USA.
  • Oloniniyi OK; Bioqual, Inc., Rockville, MD 20850, USA.
  • Zhou T; Department of Pediatrics, Emory Vaccine Center, Emory National Primate Research Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Moliva JI; Modex Therapeutics Inc., an OPKO Health Company, Natick, MA 01760, USA.
  • Zhao B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Choe M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Yang ES; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Zhang Y; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Boruszczak M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Chen M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Leung K; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Li J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Yang ZY; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Andersen H; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Carlton K; Modex Therapeutics Inc., an OPKO Health Company, Natick, MA 01760, USA.
  • Godbole S; Modex Therapeutics Inc., an OPKO Health Company, Natick, MA 01760, USA.
  • Harris DR; Bioqual, Inc., Rockville, MD 20850, USA.
  • Henry AR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Ivleva VB; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Lei P; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Liu C; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Longobardi L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Merriam JS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Nase D; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Olia AS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Pessaint L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Porto M; Bioqual, Inc., Rockville, MD 20850, USA.
  • Shi W; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Wolff JJ; Bioqual, Inc., Rockville, MD 20850, USA.
  • Douek DC; Bioqual, Inc., Rockville, MD 20850, USA.
  • Suthar MS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Gall J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Koup RA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Kwong PD; Department of Pediatrics, Emory Vaccine Center, Emory National Primate Research Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Nabel GJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Sullivan NJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
bioRxiv ; 2022 Nov 21.
Article en En | MEDLINE | ID: mdl-35982683
Despite effective countermeasures, SARS-CoV-2 persists worldwide due to its ability to diversify and evade human immunity1. This evasion stems from amino-acid substitutions, particularly in the receptor-binding domain of the spike, that confer resistance to vaccines and antibodies 2-16. To constrain viral escape through resistance mutations, we combined antibody variable regions that recognize different receptor binding domain (RBD) sites17,18 into multispecific antibodies. Here, we describe multispecific antibodies, including a trispecific that prevented virus escape >3000-fold more potently than the most effective clinical antibody or mixtures of the parental antibodies. Despite being generated before the evolution of Omicron, this trispecific antibody potently neutralized all previous variants of concern and major Omicron variants, including the most recent BA.4/BA.5 strains at nanomolar concentrations. Negative stain electron microscopy revealed that synergistic neutralization was achieved by engaging different epitopes in specific orientations that facilitated inter-spike binding. An optimized trispecific antibody also protected Syrian hamsters against Omicron variants BA.1, BA.2 and BA.5, each of which uses different amino acid substitutions to mediate escape from therapeutic antibodies. Such multispecific antibodies decrease the likelihood of SARS-CoV-2 escape, simplify treatment, and maximize coverage, providing a strategy for universal antibody therapies that could help eliminate pandemic spread for this and other pathogens.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos