ADCC: An underappreciated correlate of cross-protection against influenza?

Rory D. de Vries, Katja Hoschler, Guus F. Rimmelzwaan*

*Corresponding author for this work

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In this short review, we summarized the results obtained with an assay to detect influenza virus-specific antibodies that mediate ADCC, which was developed and evaluated within the framework of the IMI-funded project “FLUCOP”. HA-specific ADCC mediating antibodies were detected in serum samples from children and adults pre- and post-vaccination with monovalent, trivalent, or quadrivalent seasonal influenza vaccines, or following infection with H1N1pdm09 virus. Additionally, using chimeric influenza HA proteins, the presence of HA-stalk-specific ADCC mediating antibodies after vaccination and natural infection with H1N1pdm09 virus was demonstrated. With serum samples obtained from children that experienced a primary infection with an influenza B virus, we showed that primary infection induces HA-specific ADCC-mediating antibodies that cross-reacted with HA from influenza B viruses from the heterologous lineage. These cross-reactive antibodies were found to be directed to the HA stalk region. Antibodies directed to the influenza B virus HA head mediated low levels of ADCC. Finally, vaccination with a recombinant modified vaccinia virus Ankara expressing the HA gene of a clade 1 A(H5N1) highly pathogenic avian influenza virus led to the induction of ADCC-mediating antibodies, which cross-reacted with H5 viruses of antigenically distinct clades. Taken together, it is clear that virus-specific antibodies induced by infection or vaccination have immunological functionalities in addition to neutralization. These functionalities could contribute to protective immunity. The functional profiling of vaccine-induced antibodies may provide further insight into the effector functions of virus-specific antibodies and their contribution to virus-specific immunity.

Original languageEnglish
Article number1130725
JournalFrontiers in Immunology
Publication statusPublished - 22 Feb 2023

Bibliographical note

Funding Information:
This work was financially supported by Innovative Medicines Initiative (IMI) grant 115672-3 (FLUCOP). GFR received financial support from the Alexander von Humboldt Foundation in the framework of the Alexander von Humboldt Professorship endowed by the German Federal Ministry of Education and Research. This Open Access publication was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491094227 "Open Access Publication Funding" and the University of Veterinary Medicine Hannover, Foundation. Acknowledgments

Publisher Copyright:
Copyright © 2023 de Vries, Hoschler and Rimmelzwaan.


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