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  • Live Imaging of SARS-CoV-2 Infection in Mice Reveals Neutralizing Antibodies Require Fc Function for Optimal Efficacy.

Live Imaging of SARS-CoV-2 Infection in Mice Reveals Neutralizing Antibodies Require Fc Function for Optimal Efficacy.

bioRxiv : the preprint server for biology (2021-04-02)
Irfan Ullah, Jérémie Prévost, Mark S Ladinsky, Helen Stone, Maolin Lu, Sai Priya Anand, Guillaume Beaudoin-Bussières, Kelly Symmes, Mehdi Benlarbi, Shilei Ding, Romain Gasser, Corby Fink, Yaozong Chen, Alexandra Tauzin, Guillaume Goyette, Catherine Bourassa, Halima Medjahed, Matthias Mack, Kunho Chung, Craig B Wilen, Gregory A Dekaban, Jimmy D Dikeakos, Emily A Bruce, Daniel E Kaufmann, Leonidas Stamatatos, Andrew T McGuire, Jonathan Richard, Marzena Pazgier, Pamela J Bjorkman, Walther Mothes, Andrés Finzi, Priti Kumar, Pradeep D Uchil
PMID33791699
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 in prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. We could visualize virus spread sequentially from the nasal cavity to the lungs and thereafter systemically to various organs including the brain, which culminated 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 Fab-mediated neutralization, 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.