Journal
IMMUNITY
Volume 54, Issue 9, Pages 2143-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2021.08.015
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Funding
- NIH [R01AI163395, P20GM125498]
- le Ministe re de l'Economie et de l'Innovation du Quebec, Programme de soutien aux organismes de recherche et d'innovation, Foundation du CHUM
- Canadian Institutes of Health Research (CIHR) [352417]
- Rapid Research Funding Opportunity [FRN440388]
- Canada's COVID-19 Immunity Task Force (CITF)
- Canada Foundation for Innovation (CFI) [41027, 36287]
- FRQS Merit Research Scholarship
- MITACS Acceleration postdoctoral fellowship
- Fred Hutch COVID-19 Research Fund
- Canada Research Chair on Retroviral Entry [RCHS0235 950-232424]
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Neutralizing antibodies are effective in treating COVID-19, but the mechanism of immune protection is not fully understood. Real-time imaging revealed that highly potent NAbs can prevent and resolve established infections when administered within three days. Both Fab and Fc effector functions of NAbs are essential for optimal efficacy against SARS-CoV-2.
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.
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