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A multispecific antibody confers pan-reactive SARS-CoV-2 neutralization and prevents immune escape
John Misasi; Ronnie R. Wei; Lingshu Wang; Amarendra Pegu; Chih-Jen Wei; Olamide Oloniniyi; Tongqing Zhou; Juan I Moliva; Bingchun Zhao; Misook Choe; Eun Sung Yang; Yi Zhang; Marika Boruszczak; Man Chen; Kwan Leung; Juan Li; Zhi-Yong Yang; Hanne Andersen; Kevin Carlton; Sucheta Godbole; Darcy R. Harris; Amy R Henry; Vera B. Ivleva; Paula Lei; Cuiping Liu; Lindsay Longobardi; Jonah S Merriam; Danielle Nase; Adam S. Olia; Laurent Pessaint; Maciel Porto; Wei Shi; Jeremy J Wolff; Daniel C Douek; Mehul S Suthar; Jason Gall; Richard A. Koup; Peter D. Kwong; John R. Mascola; Gary J. Nabel; Nancy J. Sullivan.
Afiliação
  • John Misasi; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Ronnie R. Wei; Modex Therapeutics Inc., an OPKO Health Company, Natick, MA 01760, USA
  • Lingshu Wang; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Amarendra Pegu; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Chih-Jen Wei; Modex Therapeutics Inc., an OPKO Health Company, Natick, MA 01760, USA
  • Olamide Oloniniyi; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Tongqing Zhou; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Juan I Moliva; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Bingchun Zhao; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Misook Choe; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Eun Sung Yang; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Yi Zhang; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Marika Boruszczak; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Man Chen; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Kwan Leung; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Juan Li; Modex Therapeutics Inc., an OPKO Health Company, Natick, MA 01760, USA.
  • Zhi-Yong Yang; Modex Therapeutics Inc., an OPKO Health Company, Natick, MA 01760, USA
  • Hanne Andersen; Bioqual Inc
  • Kevin Carlton; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Sucheta Godbole; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Darcy R. Harris; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Amy R Henry; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Vera B. Ivleva; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Paula Lei; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Cuiping Liu; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Lindsay Longobardi; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Jonah S Merriam; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Danielle Nase; Bioqual, Inc., Rockville, MD 20850, USA.
  • Adam S. Olia; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Laurent Pessaint; Bioqual, Inc., Rockville, MD 20850, USA.
  • Maciel Porto; Bioqual, Inc., Rockville, MD 20850, USA.
  • Wei Shi; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Jeremy J Wolff; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Daniel C Douek; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Mehul S Suthar; Department of Pediatrics, Emory Vaccine Center, Emory National Primate Research Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Jason Gall; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Richard A. Koup; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Peter D. Kwong; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • John R. Mascola; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Gary J. Nabel; Modex Therapeutics Inc., an OPKO Health Company, Natick, MA 01760, USA
  • Nancy J. Sullivan; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-502029
ABSTRACT
Summary ParagraphDespite 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: Disponível Coleções: Preprints Base de dados: bioRxiv Tipo de estudo: Estudo prognóstico Idioma: Inglês Ano de publicação: 2022 Tipo de documento: Preprint
Texto completo
Adicionar na Minha BVS
Imprimir
XML
Buscar no Google
Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Tipo de estudo: Estudo prognóstico Idioma: Inglês Ano de publicação: 2022 Tipo de documento: Preprint