Cell
Volume 184, Issue 15, 22 July 2021, Pages 3936-3948.e10
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Article
SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2

https://doi.org/10.1016/j.cell.2021.06.005Get rights and content
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Highlights

  • Antibody responses after SARS-CoV-2 mRNA vaccination target RBD, NTD, and S2

  • SARS-CoV-2 mRNA vaccination induces a high rate of non-neutralizing antibodies

  • Crossreactive antibodies to seasonal β-coronaviruses are induced by vaccination

  • Variant mutation N501Y enhances affinity to human ACE2 while E484K reduces it

Summary

In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast-derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to spikes of seasonal human coronaviruses OC43 and HKU1. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine-induced RBD binding antibodies may provide substantial protection against viral variants carrying single E484K RBD mutations.

Keywords

SARS-CoV-2
mRNA vaccination
mAbs
NTD
RBD
spike
plasmablasts

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