TY - JOUR
T1 - Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination
AU - Clark, Jordan J.
AU - Hoxie, Irene
AU - Adelsberg, Daniel C.
AU - Sapse, Iden A.
AU - Andreata-Santos, Robert
AU - Yong, Jeremy S.
AU - Amanat, Fatima
AU - Tcheou, Johnstone
AU - Raskin, Ariel
AU - Singh, Gagandeep
AU - González-Domínguez, Irene
AU - Edgar, Julia E.
AU - Bournazos, Stylianos
AU - Sun, Weina
AU - Carreño, Juan Manuel
AU - Simon, Viviana
AU - Ellebedy, Ali H.
AU - Bajic, Goran
AU - Krammer, Florian
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/11/26
Y1 - 2024/11/26
N2 - Neutralizing antibodies correlate with protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection against disease progression. Non-neutralizing antibodies cannot directly protect against infection but may recruit effector cells and thus contribute to the clearance of infected cells. Additionally, they often bind conserved epitopes across multiple variants. Here, we characterize 42 human monoclonal antibodies (mAbs) from coronavirus disease 2019 (COVID-19)-vaccinated individuals. Most of these antibodies exhibit no neutralizing activity in vitro, but several non-neutralizing antibodies provide protection against lethal challenge with SARS-CoV-2 in different animal models. A subset of those mAbs shows a clear dependence on Fc-mediated effector functions. We have determined the structures of three non-neutralizing antibodies, with two targeting the receptor-binding domain and one that binds the subdomain 1 region. Our data confirm the real-world observation in humans that non-neutralizing antibodies to SARS-CoV-2 can be protective.
AB - Neutralizing antibodies correlate with protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection against disease progression. Non-neutralizing antibodies cannot directly protect against infection but may recruit effector cells and thus contribute to the clearance of infected cells. Additionally, they often bind conserved epitopes across multiple variants. Here, we characterize 42 human monoclonal antibodies (mAbs) from coronavirus disease 2019 (COVID-19)-vaccinated individuals. Most of these antibodies exhibit no neutralizing activity in vitro, but several non-neutralizing antibodies provide protection against lethal challenge with SARS-CoV-2 in different animal models. A subset of those mAbs shows a clear dependence on Fc-mediated effector functions. We have determined the structures of three non-neutralizing antibodies, with two targeting the receptor-binding domain and one that binds the subdomain 1 region. Our data confirm the real-world observation in humans that non-neutralizing antibodies to SARS-CoV-2 can be protective.
KW - ADCC
KW - ADCP
KW - CP: Immunology
KW - effector functions
KW - immunology
KW - mAbs
KW - non-neutralizing mAbs
KW - spike
UR - http://www.scopus.com/inward/record.url?scp=85208102480&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2024.114922
DO - 10.1016/j.celrep.2024.114922
M3 - Article
C2 - 39504245
AN - SCOPUS:85208102480
SN - 2639-1856
VL - 43
JO - Cell Reports
JF - Cell Reports
IS - 11
M1 - 114922
ER -