CaltechAUTHORS
  A Caltech Library Service

Live imaging of SARS-CoV-2 infection in mice reveals neutralizing antibodies require Fc function for optimal efficacy

Ullah, Irfan and Prevost, Jeremie and Ladinsky, Mark S. and Stone, Helen and Lu, Maolin and Anand, Sai Priya and Beaudoin-Bussieres, Guillaume 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 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 neutralizing antibodies require Fc function for optimal efficacy. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20210323-080814224

[img] PDF - Submitted Version
See Usage Policy.

17Mb
[img] PDF (Supplementary figures 1-7) - Supplemental Material
See Usage Policy.

33Mb
[img] Video (MPEG) (Video S1, Supplemental movie for Figure 1) - Supplemental Material
See Usage Policy.

5Mb
[img] Video (QuickTime) (Video S2, Supplemental movie for Figure 2) - Supplemental Material
See Usage Policy.

16Mb
[img] Video (QuickTime) (Video S3, Supplemental movie for Figure 2) - Supplemental Material
See Usage Policy.

13Mb
[img] Video (QuickTime) (Video S4, Supplemental movie for Figure 2) - Supplemental Material
See Usage Policy.

10Mb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20210323-080814224

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 visualized sequential spread of virus from the nasal cavity to the lungs followed by systemic spread 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 of infection. In addition to direct neutralization, in vivo efficacy required Fc effector functions of NAbs, with contributions from monocytes, neutrophils and natural killer cells, to dampen inflammatory responses and limit immunopathology. Thus, our study highlights the requirement of both Fab and Fc effector functions for an optimal in vivo efficacy afforded by NAbs against SARS-CoV-2.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2021.03.22.436337DOIDiscussion Paper
ORCID:
AuthorORCID
Ullah, Irfan0000-0002-7760-8693
Ladinsky, Mark S.0000-0002-1036-3513
Stone, Helen0000-0002-3344-5079
Lu, Maolin0000-0002-8099-6447
Anand, Sai Priya0000-0001-9821-8259
Beaudoin-Bussieres, Guillaume0000-0002-8092-4101
Gasser, Romain0000-0002-8565-1106
Tauzin, Alexandra0000-0001-9153-3600
Goyette, Guillaume0000-0003-3277-568X
Wilen, Craig B0000-0003-2495-9403
Dikeakos, Jimmy D0000-0001-8141-5395
Stamatatos, Leonidas0000-0002-1106-7097
McGuire, Andrew0000-0003-1841-6859
Richard, Jonathan0000-0002-9015-9589
Pazgier, Marzena0000-0003-0594-5057
Bjorkman, Pamela J.0000-0002-2277-3990
Mothes, Walther0000-0002-3367-7240
Finzi, Andres0000-0002-4992-5288
Kumar, Priti0000-0002-6901-5601
Uchil, Pradeep D0000-0002-7236-858X
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. This version posted March 22, 2021. This work was supported by NIH grants P50AI150464 to WM and PJB; R33AI122384 and RO1AI145164 to PK; George Mason University Fast Grants to MSL and PJB; P20GM125498 (awarded to UVM Translational Global Infectious Disease Research Center) to EAB; le Ministère de l’Économie et de l’Innovation du Québec, Programme de soutien aux organismes de recherche et d’innovation, Foundation du CHUM, Canadian Institutes of Health Research (CIHR) foundation grant #352417 & Rapid Research Funding Opportunity #FRN440388 to J.D.D. and G.A.D, Canada Research Chair on Retroviral Entry no. RCHS0235 950-232424 to AF; Canada’s COVID-19 Immunity Task Force (CITF) & Canada Foundation for Innovation (CFI) #41027 to AF and DEK & #36287 to JDD. and GAD; FRQS Merit Research Scholarship to DEK; CIHR fellowships to JP, SPA and GBB, MITACS Accélération postdoctoral fellowship to RG; Fred Hutch COVID-19 Research Fund to LS and ATM. Author Contributions: PDU, IU, JP, PK, AF, & WM: conceptualization, 392 experimental design, interpretation, and manuscript preparation and writing; IU: animal experiments, BLI, antibody biodistribution, viral load analyses & data processing; PDU: histological analyses, FACS, data processing, figure generation & initial draft; LS & ATM: isolated NAbs; JP, ML, SPA, GBB, MB, SD, RG, CF, YC, AT, GG, CB, HM, GAD, JDD, DEK, JR, MP, WM and AF: generation & in vitro characterization of SARS-CoV-2 S NAbs; MSL & PJB: EM tomography; IU, HS: cytokine, N gene mRNA PCR; MM: anti-CCR2 antibody; CBW: aliquot of the reporter virus. PK, WM, AF, PJB: funding for the work. Disclaimer: The views expressed in this presentation are those of the authors and do not reflect the official policy or position of the Uniformed Services University, US Army, the Department of Defense, or the US Government. The authors have declared no competing interest.
Group:COVID-19
Funders:
Funding AgencyGrant Number
NIHP50AI150464
NIHR33AI122384
NIHRO1AI145164
George Mason UniversityUNSPECIFIED
NIHP20GM125498
le Ministère de l’Économie et de l’Innovation du QuébecUNSPECIFIED
Programme de soutien aux organismes de recherche et d’innovationUNSPECIFIED
Foundation du CHUMUNSPECIFIED
Canadian Institutes of Health Research (CIHR)352417
Rapid Research Funding OpportunityFRN440388
Canada Research Chairs ProgramRCHS0235 950-232424
Canada COVID-19 Immunity Task Force (CITF)UNSPECIFIED
Canada Foundation for Innovation41027
Canada Foundation for Innovation36287
Fonds de recherche du Québec – Santé (FRQS)UNSPECIFIED
MITACS Accélération Postdoctoral FellowshipUNSPECIFIED
Fred Hutch COVID-19 Research FundUNSPECIFIED
Subject Keywords:SARS-CoV-2, COVID-19, nanoluciferase, bioluminescence imaging, neutralizing antibodies, convalescent patients, human ACE2 transgenic mice, monocytes, natural killer cells, monocytes, pathogenesis, inflammatory cytokines, Fc effector functions
Record Number:CaltechAUTHORS:20210323-080814224
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210323-080814224
Official Citation:Live imaging of SARS-CoV-2 infection in mice reveals neutralizing antibodies require Fc function for optimal efficacy. Irfan Ullah, Jeremie Prevost, Mark S. Ladinsky, Helen Stone, Maolin Lu, Sai Priya Anand, Guillaume Beaudoin-Bussieres, 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 McGuire, Jonathan Richard, Marzena Pazgier, Pamela Bjorkman, Walther Mothes, Andres Finzi, Priti Kumar, Pradeep D Uchil. bioRxiv 2021.03.22.436337; doi: https://doi.org/10.1101/2021.03.22.436337
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108524
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:23 Mar 2021 17:24
Last Modified:19 Apr 2021 22:05

Repository Staff Only: item control page