Eur J Immunol . Natural killer cell-mediated ADCC in SARS-CoV-2-infected individuals and vaccine recipients

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Eur J Immunol


. 2022 Apr 13.
doi: 10.1002/eji.202149470. Online ahead of print.
Natural killer cell-mediated ADCC in SARS-CoV-2-infected individuals and vaccine recipients


Kerri Hagemann ¹ , Kristoffer Riecken ² , Johannes Jung ¹ , Heike Hildebrandt ¹ , Stephan Menzel ³ , Madeleine Bunders ⁴ , Boris Fehse ^{2 5} , Friedrich Koch-Nolte ³ , Fabian Heinrich ^{6 7} , Sven Peine ⁸ , Julian Schulze Zur Wiesch ^{5 9} , Thomas T Brehm ^{5 9} , Marylyn M Addo ^{5 9 10} , Marc Lütgehetmann ⁶ , Marcus Altfeld ^{1 5}



Affiliations

• PMID: 35416291
• DOI: 10.1002/eji.202149470

Abstract

COVID-19, caused by SARS-CoV-2, has emerged as a global pandemic. While immune responses of the adaptive immune system have been in the focus of research, the role of NK cells in COVID-19 remains less well understood. Here we characterized NK cell-mediated SARS-CoV-2 antibody-dependent cellular cytotoxicity (ADCC) against SARS-CoV-2 spike-1 (S1) and nucleocapsid (NC) protein. Serum samples from SARS-CoV-2 resolvers induced significant CD107a-expression by NK cells in response to S1 and NC, while serum samples from SARS-CoV-2-negative individuals did not. Furthermore, serum samples from individuals that received the BNT162b2 vaccine induced strong CD107a-expression by NK cells that increased with the second vaccination and was significantly higher than observed in infected individuals. As expected, vaccine-induced responses were only directed against S1 and not against NC protein. S1-specific CD107a responses by NK cells were significantly correlated to NK cell-mediated killing of S1-expressing cells. Interestingly, screening of serum samples collected prior to the COVID-19 pandemic identified two individuals with cross-reactive antibodies against SARS-CoV-2 S1, which also induced degranulation of NK cells. Taken together, these data demonstrate that antibodies induced by SARS-CoV-2 infection and anti-SARS-CoV-2 vaccines can trigger significant NK cell-mediated ADCC activity, and identify some cross-reactive ADCC-activity against SARS-CoV-2 by endemic coronavirus-specific antibodies. This article is protected by copyright. All rights reserved.

Keywords: ADCC; COVID-19; NK cells; innate immunity; vaccine.