ADCC antibodies are a protective immune correlate in a household model of influenza transmission
Sophie A Valkenburg, Athena Li, Nancy HL Leung, Leo LM Poon, and Benjamin Cowling School of Public Health, The University of Hong Kong, Hong Kong
Immune correlates of protection need to be defined for the development of next generation influenza vaccines. Cross reactive antibodies which engage NK cells, to mediate Antibody Dependent Cellular cytotoxicity (ADCC), have been shown to be increased in older adults accounting for reduced H1N1 pandemic infection and risk of infection in a human challenge study, whilst also showing evidence for cross reactivity to avian viruses. Our study reports on the context of household acquired infection in the Hong Kong community, and baseline PBMC and serum samples were collected from households reporting an index case of infection. Contacts of infected subjects were recruited and monitored for acquisition of infection. The baseline ADCC influenza-specific responses of uninfected contacts was found to be higher in magnitude and avidity to multiple influenza proteins than infected contacts, indicating a protective role of ADCC antibodies in the acquisition of influenza infection. Infection boosted ADCC responses and correlated with reduced symptoms during infection. Whilst total antibodies were higher for conserved proteins including the NP and HA-stem in uninfected subjects. This study provides rare data on the context of community acquired influenza infection and the protective threshold of baseline immune responses for ADCC antibodies.
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