National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
P01 AI110657
米国
引用
ジャーナル: Cell Host Microbe / 年: 2021 タイトル: A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection. 著者: Hejun Liu / Meng Yuan / Deli Huang / Sandhya Bangaru / Fangzhu Zhao / Chang-Chun D Lee / Linghang Peng / Shawn Barman / Xueyong Zhu / David Nemazee / Dennis R Burton / Marit J van Gils / ...著者: Hejun Liu / Meng Yuan / Deli Huang / Sandhya Bangaru / Fangzhu Zhao / Chang-Chun D Lee / Linghang Peng / Shawn Barman / Xueyong Zhu / David Nemazee / Dennis R Burton / 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 / 要旨: Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking ...Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown 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. Recognition of the N343 glycosylation site and water-mediated interactions facilitate cross-reactivity of CV38-142 to SARS-related viruses, allowing the antibody to accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, notably COVA1-16, to enhance neutralization of SARS-CoV and SARS-CoV-2, including circulating variants of concern B.1.1.7 and B.1.351. 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 SARS-related coronaviruses.