RT Journal Article
SR Electronic
T1 Live imaging of SARS-CoV-2 infection in mice reveals neutralizing antibodies require Fc function for optimal efficacy
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.22.436337
DO 10.1101/2021.03.22.436337
A1 Irfan Ullah
A1 Jérémie Prévost
A1 Mark S Ladinsky
A1 Helen Stone
A1 Maolin Lu
A1 Sai Priya Anand
A1 Guillaume Beaudoin-Bussières
A1 Mehdi Benlarbi
A1 Shilei Ding
A1 Romain Gasser
A1 Corby Fink
A1 Yaozong Chen
A1 Alexandra Tauzin
A1 Guillaume Goyette
A1 Catherine Bourassa
A1 Halima Medjahed
A1 Matthias Mack
A1 Kunho Chung
A1 Craig B Wilen
A1 Gregory A. Dekaban
A1 Jimmy D. Dikeakos
A1 Emily A. Bruce
A1 Daniel E Kaufmann
A1 Leonidas Stamatatos
A1 Andrew T. McGuire
A1 Jonathan Richard
A1 Marzena Pazgier
A1 Pamela J. Bjorkman
A1 Walther Mothes
A1 Andrés Finzi
A1 Priti Kumar
A1 Pradeep D. Uchil
YR 2021
UL http://biorxiv.org/content/early/2021/03/22/2021.03.22.436337.abstract
AB Neutralizing antibodies (NAbs) are effective in treating COVID-19 but the mechanism of immune protection is not fully understood. Here, we applied live bioluminescence imaging (BLI) to monitor the real-time effects of NAb treatment in prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. We visualized sequential spread of virus from the nasal cavity to the lungs followed by systemic spread to various organs including the brain, culminating in death. Highly potent NAbs from a COVID-19 convalescent subject prevented, and also effectively resolved, established infection when administered within three days of infection. In addition to direct neutralization, in vivo efficacy required Fc effector functions of NAbs, with contributions from monocytes, neutrophils and natural killer cells, to dampen inflammatory responses and limit immunopathology. Thus, our study highlights the requirement of both Fab and Fc effector functions for an optimal in vivo efficacy afforded by NAbs against SARS-CoV-2.Competing Interest StatementThe authors have declared no competing interest.