tetano
Editor, Senior Moderator
Cell Rep
. 2022 Jan 25;110368.
doi: 10.1016/j.celrep.2022.110368. Online ahead of print.
A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection
Guillaume Beaudoin-Bussières[SUP] 1 [/SUP], Yaozong Chen[SUP] 2 [/SUP], Irfan Ullah[SUP] 3 [/SUP], Jérémie Prévost[SUP] 1 [/SUP], William D Tolbert[SUP] 2 [/SUP], Kelly Symmes[SUP] 3 [/SUP], Shilei Ding[SUP] 4 [/SUP], Mehdi Benlarbi[SUP] 4 [/SUP], Shang Yu Gong[SUP] 5 [/SUP], Alexandra Tauzin[SUP] 1 [/SUP], Romain Gasser[SUP] 1 [/SUP], Debashree Chatterjee[SUP] 4 [/SUP], Dani Vézina[SUP] 4 [/SUP], Guillaume Goyette[SUP] 4 [/SUP], Jonathan Richard[SUP] 1 [/SUP], Fei Zhou[SUP] 6 [/SUP], Leonidas Stamatatos[SUP] 7 [/SUP], Andrew T McGuire[SUP] 8 [/SUP], Hughes Charest[SUP] 9 [/SUP], Michel Roger[SUP] 10 [/SUP], Edwin Pozharski[SUP] 11 [/SUP], Priti Kumar[SUP] 3 [/SUP], Walther Mothes[SUP] 12 [/SUP], Pradeep D Uchil[SUP] 13 [/SUP], Marzena Pazgier[SUP] 14 [/SUP], Andrés Finzi[SUP] 15 [/SUP]
Affiliations
Abstract
Emerging evidence indicates that both neutralizing and Fc-mediated effector functions of antibodies contribute to protection against SARS-CoV-2. It is unclear whether Fc-effector functions alone can protect against SARS-CoV-2. Here, we isolated CV3-13, a non-neutralizing antibody, from a convalescent individual with potent Fc-mediated effector functions. The cryoelectron microscopy structure of CV3-13 in complex with the SARS-CoV-2 spike reveals that the antibody binds from a distinct angle of approach to an N-terminal domain (NTD) epitope that only partially overlaps with the NTD supersite recognized by neutralizing antibodies. CV3-13 does not alter the replication dynamics of SARS-CoV-2 in K18-hACE2 mice, but its Fc-enhanced version significantly delays virus spread, neuroinvasion, and death in prophylactic settings. Interestingly, the combination of Fc-enhanced non-neutralizing CV3-13 with Fc-compromised neutralizing CV3-25 completely protects mice from lethal SARS-CoV-2 infection. Altogether, our data demonstrate that efficient Fc-mediated effector functions can potently contribute to the in vivo efficacy of anti-SARS-CoV-2 antibodies.
Keywords: ADCC; COVID-19; Fc-effector functions; K18-hACE2 mice; SARS-CoV-2; coronavirus; non-neutralizing antibodies; spike; synergy.
. 2022 Jan 25;110368.
doi: 10.1016/j.celrep.2022.110368. Online ahead of print.
A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection
Guillaume Beaudoin-Bussières[SUP] 1 [/SUP], Yaozong Chen[SUP] 2 [/SUP], Irfan Ullah[SUP] 3 [/SUP], Jérémie Prévost[SUP] 1 [/SUP], William D Tolbert[SUP] 2 [/SUP], Kelly Symmes[SUP] 3 [/SUP], Shilei Ding[SUP] 4 [/SUP], Mehdi Benlarbi[SUP] 4 [/SUP], Shang Yu Gong[SUP] 5 [/SUP], Alexandra Tauzin[SUP] 1 [/SUP], Romain Gasser[SUP] 1 [/SUP], Debashree Chatterjee[SUP] 4 [/SUP], Dani Vézina[SUP] 4 [/SUP], Guillaume Goyette[SUP] 4 [/SUP], Jonathan Richard[SUP] 1 [/SUP], Fei Zhou[SUP] 6 [/SUP], Leonidas Stamatatos[SUP] 7 [/SUP], Andrew T McGuire[SUP] 8 [/SUP], Hughes Charest[SUP] 9 [/SUP], Michel Roger[SUP] 10 [/SUP], Edwin Pozharski[SUP] 11 [/SUP], Priti Kumar[SUP] 3 [/SUP], Walther Mothes[SUP] 12 [/SUP], Pradeep D Uchil[SUP] 13 [/SUP], Marzena Pazgier[SUP] 14 [/SUP], Andrés Finzi[SUP] 15 [/SUP]
Affiliations
- PMID: 35123652
- DOI: 10.1016/j.celrep.2022.110368
Abstract
Emerging evidence indicates that both neutralizing and Fc-mediated effector functions of antibodies contribute to protection against SARS-CoV-2. It is unclear whether Fc-effector functions alone can protect against SARS-CoV-2. Here, we isolated CV3-13, a non-neutralizing antibody, from a convalescent individual with potent Fc-mediated effector functions. The cryoelectron microscopy structure of CV3-13 in complex with the SARS-CoV-2 spike reveals that the antibody binds from a distinct angle of approach to an N-terminal domain (NTD) epitope that only partially overlaps with the NTD supersite recognized by neutralizing antibodies. CV3-13 does not alter the replication dynamics of SARS-CoV-2 in K18-hACE2 mice, but its Fc-enhanced version significantly delays virus spread, neuroinvasion, and death in prophylactic settings. Interestingly, the combination of Fc-enhanced non-neutralizing CV3-13 with Fc-compromised neutralizing CV3-25 completely protects mice from lethal SARS-CoV-2 infection. Altogether, our data demonstrate that efficient Fc-mediated effector functions can potently contribute to the in vivo efficacy of anti-SARS-CoV-2 antibodies.
Keywords: ADCC; COVID-19; Fc-effector functions; K18-hACE2 mice; SARS-CoV-2; coronavirus; non-neutralizing antibodies; spike; synergy.