Primary Human Influenza B Virus Infection Induces Cross-Lineage Hemagglutinin Stalk–Specific Antibodies Mediating Antibody-Dependent Cellular Cytoxicity
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Influenza A virus (IAV) and influenza B virus (IBV) cause substantial morbidity and mortality during annual epidemics. Two distinct lineages of IBV are distinguished, based on variation in hemagglutinin (HA): B/Victoria/2/87-like (B/Vic) and B/Yamagata/16/88-like (B/Yam). Here, we show that, in humans, primary IBV infection with either lineage induces HA-specific antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. IBV infection induced antibodies specific to the HA head and stalk, but only HA stalk-specific antibodies mediated ADCC efficiently and displayed cross-reactivity with IBV of both lineages. This corresponds to recent findings that 2 points of contact between the effector and target cell (ie, HA and sialic acid, respectively, and the fragment crystallizable [Fc] domain and Fcγ receptor IIIα, respectively) are required for efficient ADCC activity and that antibodies specific for the receptor-binding site located in the head domain of HA therefore fail to mediate ADCC. Potentially, ADCC-mediating antibodies directed to the HA stalk of IBV contribute to cross-protective immunity to IBV of both lineages.
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ADCC is mainly mediated by the interaction between virus-specific antibodies and Fcγ receptor IIIα (FcγRIIIα, CD16), which is present on NK cells.
“ADCC is mainly mediated by the interaction between virus-specific antibodies and Fcγ receptor IIIα (FcγRIIIα, CD16), which is, for example, present on NK cells (61–63).”
From SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients (2021) · cites this paper as [62]
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- Authors
- de Vries, R. D., Nieuwkoop, N. J., van der Klis, F. R. M., Koopmans, M. P. G., Krammer, F., & Rimmelzwaan, G. F.
- Affiliations
- Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
- Erasmus MC (NL)
- Center for Infectious Disease Control, National Institute of Public Health and the Environment, Bilthoven, the Netherlands
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Rimmelzwaan, Guus F
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-12-22
- Volume
- 217
- Issue
- 1
- Pages
- 3-11
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC5853962
- OpenAlex
- W2777561423
- Cited by
- 39
- References
- 42
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 7 · 2019: 8 · 2018: 7 · 2017: 1
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Rivm Repository (Netherlands National Institute for Public Health and the Environment) (submittedVersion)
- Rivm (National Institute for Public Health and the Environment) (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (U19 AI109946)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- influenza B, hemagglutinin stalk, antibody-dependent cellular cytotoxicity, primary infection, cross-protective immunity, sialic acid, receptor binding sites, humoral immunity
- MeSH terms
- Antibodies, Viral, Antibody-Dependent Cell Cytotoxicity, Child, Child, Preschool, Cross Reactions, Cross-Sectional Studies, Female, Genotype, Humans, Infant, Influenza, Human, Male, Influenza B virus, Hemagglutinin Glycoproteins, Influenza Virus
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