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TitleProtective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination.
Journal, issue, pagesCell Rep, Vol. 43, Issue 11, Page 114922, Year 2024
Publish dateNov 5, 2024
AuthorsJordan J Clark / Irene Hoxie / Daniel C Adelsberg / Iden A Sapse / Robert Andreata-Santos / Jeremy S Yong / Fatima Amanat / Johnstone Tcheou / Ariel Raskin / Gagandeep Singh / Irene González-Domínguez / Julia E Edgar / Stylianos Bournazos / Weina Sun / Juan Manuel Carreño / Viviana Simon / Ali H Ellebedy / Goran Bajic / Florian Krammer /
PubMed AbstractNeutralizing 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 ...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.
External linksCell Rep / PubMed:39504245 / PubMed Central
MethodsEM (single particle)
Resolution3.42 - 4.31 Å
Structure data

43255

8via

EMDB-43255, PDB-8via:
Protective effect of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-43306: cryo-EM structure of a non-neutralizing antibody V3-21 in complex with SARS-CoV-2 spike
Method: EM (single particle) / Resolution: 4.31 Å

EMDB-43314: cryo-EM structure of a non-neutralizing antibody V6-12 in complex with SARS-CoV-2 spike
Method: EM (single particle) / Resolution: 3.42 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
KeywordsIMMUNE SYSTEM / antibody / SARS-CoV-2 / spike

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