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

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2021 Aug 28

PMID 34453881

Citations 131

Authors

Irfan Ullah

Jeremie Prevost

Mark S Ladinsky

Helen Stone

Maolin Lu

Sai Priya Anand

Guillaume Beaudoin-Bussieres

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

Andres Finzi

Priti Kumar

Pradeep D Uchil

Affiliations

Soon will be listed here.

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.

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