Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 217, Issue 1, Pages 3-11Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jix546
Keywords
Influenza B virus; hemagglutinin; antibodies; natural killer cells; antibody-dependent cellular cytotoxicity
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Funding
- Innovative Medicines Initiative (FLUCOP grant) [115672-3]
- National Institute of Allergy and Infectious Diseases [U19 AI109946]
- European Union (FLUNIVAC grant) [602604]
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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/16/88like (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 Fc. receptor IIIa, 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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