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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, pagesbioRxiv, Year 2024
Publish dateMar 1, 2024
AuthorsJordan 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 SARS-CoV-2. Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with ...Neutralizing antibodies correlate with protection against SARS-CoV-2. Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection from disease progression. Non-neutralizing antibodies cannot directly protect from infection but may recruit effector cells thus contribute to the clearance of infected cells. Also, they often bind conserved epitopes across multiple variants. We characterized 42 human mAbs from COVID-19 vaccinated individuals. Most of these antibodies exhibited no neutralizing activity but several non-neutralizing antibodies protected against lethal challenge with SARS-CoV-2 in different animal models. A subset of those mAbs showed a clear dependence on Fc-mediated effector functions. We determined the structures of three non-neutralizing antibodies with two targeting the RBD, and one that targeting the SD1 region. Our data confirms the real-world observation in humans that non-neutralizing antibodies to SARS-CoV-2 can be protective.
External linksbioRxiv / PubMed:38464151 / PubMed Central
MethodsEM (single particle)
Resolution3.6 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

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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