A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection

Hejun Liu, Meng Yuan, Deli Huang, Sandhya Bangaru, Chang-Chun D. Lee, Linghang Peng, Xueyong Zhu, David Nemazee, Marit J. van Gils, Rogier W. Sanders, Hans-Christian Kornau, S. Momsen Reincke, Harald Prüss, Jakob Kreye, Nicholas C. Wu, Andrew B. Ward, Ian A. Wilson

Research output: Working paper

Abstract

Coronaviruses have caused several epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Some prophylactic vaccines and therapeutic antibodies have already showed striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses. Cross-neutralizing antibodies to SARS-related viruses provide opportunities to address such concerns. Here, we report on crystal structures of a cross-neutralizing antibody CV38-142 in complex with the receptor binding domains from SARS-CoV-2 and SARS-CoV. Our structural findings provide mechanistic insights into how this antibody can accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, in particular COVA1-16, to enhance neutralization of SARS-CoV-2 and SARS-CoV. Overall, this study provides valuable information for vaccine and therapeutic design to address current and future antigenic drift in SARS-CoV-2 and to protect against zoonotic coronaviruses.Competing Interest StatementA patent application for SARS-CoV-2 antibody CV38-142 was first disclosed in (Kreye et al, 2020) and filed under application number 20182069.3 by some of the authors at Neurodegenerative Diseases (DZNE) and Charite-Universitatsmedizin Berlin. The Amsterdam UMC filed a patent on SARS-CoV-2 antibodies including COVA1-16 under application number 2020-039EP-PR that included the AMC authors on this paper.
Original languageEnglish (US)
PublisherCold Spring Harbor Laboratory Press
Number of pages57
DOIs
StateIn preparation - Feb 12 2021

Publication series

NamebioRxiv
PublisherCold Spring Harbor Laboratory Press

Keywords

  • Coronavirus
  • COVID-19
  • severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
  • Novel coronavirus
  • 2019-nCoV
  • Pandemic

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