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.
【저자키워드】 COVID-19, SARS-CoV-2, coronavirus, spike, K18-hACE2 mice, ADCC, synergy, Fc-effector functions, Non-neutralizing antibodies, 【초록키워드】 Efficacy, Neutralizing antibodies, antibody, SARS-COV-2 infection, Prophylactic, Replication, anti-SARS-CoV-2 antibodies, mice, Microscopy, death, Neutralizing, NTD, convalescent, in vivo, epitope, synergy, function, K18-hACE2, N-terminal domain, Evidence, Combination, Fc-mediated effector function, overlap, virus spread, complex, Fc-mediated effector functions, Alter, approach, bind, PROTECT, significantly, indicate, contribute, reveal, non-neutralizing antibody, the SARS-CoV-2, 【제목키워드】 SARS-COV-2 infection, mice, NAb, virus spread, PROTECT, non-neutralizing antibody,