Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy
- DOI
- Language of the publication
- English
- Date
- 2021-08-18
- Type
- Accepted manuscript
- Author(s)
- Ullah, Irfan
- Prévost, Jérémie
- Ladinsky, Mark S.
- Stone, Helen
- Lu, Maolin
- Anand, Sai Priya
- Beaudoin-Bussières, Guillaume
- Symmes, Kelly
- Benlarbi, Mehdi
- Ding, Shilei
- Gasser, Romain
- Fink, Corby
- Chen, Yaozong
- Tauzin, Alexandra
- Goyette, Guillaume
- Bourassa, Catherine
- Medjahed, Halima
- Mack, Matthias
- Chung, Kunho
- Wilen, Craig B.
- Dekaban, Gregory A.
- Dikeakos, Jimmy D.
- Bruce, Emily A.
- Kaufmann, Daniel E.
- Stamatatos, Leonidas
- McGuire, Andrew T.
- Richard, Jonathan
- Pazgier, Marzena
- Bjorkman, Pamela J.
- Mothes, Walther
- Finzi, Andrés
- Kumar, Priti
- Uchil, Pradeep D.
- Publisher
- Cell Press
Abstract
HIGHLIGHTS •BLI enables real-time monitoring of SARS-CoV-2 spread in vivo •SARS-CoV-2 NAbs require Fc effector function for prophylaxis and therapy •FcγR engagement by NAbs reduces virus load and limits immunopathology •Monocytes, neutrophils, and NK cells contribute to Fc-dependent NAb protection SUMMARY 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 during prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. Real-time imaging revealed that the virus spread sequentially from the nasal cavity to the lungs in mice and thereafter systemically 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. In addition to direct neutralization, depletion studies indicated that Fc effector interactions of NAbs with monocytes, neutrophils, and natural killer cells were required to effectively dampen inflammatory responses and limit immunopathology. Our study highlights that both Fab and Fc effector functions of NAbs are essential for optimal in vivo efficacy against SARS-CoV-2.
Description
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Subject
- Health
Keywords
- COVID-19,
- Fc effector functions,
- SARS-CoV-2,
- bioluminescence imaging,
- human ACE2 transgenic mice,
- monocytes,
- nanoluciferase,
- natural killer cells,
- neutralizing antibodies,
- pathogenesis,
- inflammatory cytokines,
- convalescent patients
Rights
Pagination
2143-2158
Peer review
Yes
Open access level
Green
Identifiers
- ISSN
- 1074-7613
Article
- Journal title
- Immunity
- Journal volume
- 54
- Journal issue
- 9
- Article number
- e15
- Accepted date
- 2021-08-11
Citation(s)
1.Ullah I, Prévost J, Ladinsky MS, et al. Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy. Immunity. 2021;54(9):2143-2158.e15. doi:https://doi.org/10.1016/j.immuni.2021.08.015