Ullah, Irfan and Prevost, Jeremie and Ladinsky, Mark S. and Stone, Helen and Lu, Maolin and Anand, Sai Priya and Beaudoin-Bussieres, Guillaume and Symmes, Kelly and Benlarbi, Mehdi and Ding, Shilei and Gasser, Romain and Fink, Corby and Chen, Yaozong and Tauzin, Alexandra and Goyette, Guillaume and Bourassa, Catherine and Medjahed, Halima and Mack, Matthias and Chung, Kunho and Wilen, Craig B. and Dekaban, Gregory A. and Dikeakos, Jimmy D. and Bruce, Emily A. and Kaufmann, Daniel E. and Stamatatos, Leonidas and McGuire, Andrew T. and Richard, Jonathan and Pazgier, Marzena and Bjorkman, Pamela J. and Mothes, Walther and Finzi, Andres and Kumar, Priti and Uchil, Pradeep D. (2021) Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy. IMMUNITY, 54 (9). 2143-+. ISSN 1074-7613, 1097-4180
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EFFECTOR FUNCTIONS; CONFORMATIONAL DYNAMICS; CORONAVIRUS; TOMOGRAPHY; PROTECTION; RECEPTOR; SPIKES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Sep 2022 14:03 |
| Last Modified: | 27 Sep 2022 14:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48115 |
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