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Title | 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. |
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Journal, issue, pages | Cell Rep, Vol. 38, Issue 7, Page 110368, Year 2022 |
Publish date | Feb 15, 2022 |
Authors | Guillaume Beaudoin-Bussières / Yaozong Chen / Irfan Ullah / Jérémie Prévost / William D Tolbert / Kelly Symmes / Shilei Ding / Mehdi Benlarbi / Shang Yu Gong / Alexandra Tauzin / Romain Gasser / Debashree Chatterjee / Dani Vézina / Guillaume Goyette / Jonathan Richard / Fei Zhou / Leonidas Stamatatos / Andrew T McGuire / Hughes Charest / Michel Roger / Edwin Pozharski / Priti Kumar / Walther Mothes / Pradeep D Uchil / Marzena Pazgier / Andrés Finzi / |
PubMed 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 ...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. |
External links | Cell Rep / PubMed:35123652 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.18 Å |
Structure data | EMDB-24628, PDB-7rq6: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / human non-neutralizing mAb / NTD-directed antibody / ADCC / novel NTD epitope / SARS-CoV-2 / spike / N-terminal domain / VIRAL PROTEIN-IMMUNE SYSTEM complex |