in a household study of influenza transmission
Sophie Valkenburg published in Clinical & Translational Immunology a new paper: Cross-reactive antibody-dependent cellular cytotoxicity antibodies are increased by recent infection in a household study of influenza transmission with Malik Peiris, Benjamin Cowling, Leo Poon and colleagues from the School of Public Health.
Sophie A Valkenburg , Vicky J Fang, Nancy HL Leung , Daniel KW Chu, Dennis KM Ip, Ranawaka APM Perera, Yizhuo Wang, Athena PY Li, JS Malik Peiris, Benjamin J Cowling & Leo LM Poon.
PMID: 31763042 PMCID: PMC6864499 DOI: 10.1002/cti2.1092
Objectives. Influenza causes a spectrum of disease from asymptomatic infection to fatal outcome, and pre-existing immunity can alter susceptibility and disease severity. In a household transmission study, we recruited outpatients with confirmed influenza virus infection and prospectively identified secondary infections in their household contacts, therefore identifying infection cases with baseline samples for determining immune-mediated protection from influenza infection.
Methods. We examined baseline broadly reactive immune correlates of relevance to universal vaccine development, specifically antibody- dependent cytotoxic (ADCC) antibodies and T-cell responses in functional assays. Antibodies were assessed in a cell-based NK cell degranulation assay by flow cytometry, and T-cell responses were assessed by IFN-c intracellular cytokine staining flow cytometry assay.
Results. The magnitude of antibody responses and ADCC function for multiple influenza-specific proteins was lower in participants who became infected, consolidating the role of pre- existing antibodies in protection from seasonal influenza virus infection. Among H1N1-infected contacts, we found that higher levels of pre-existing H1-haemagglutinin ADCC responses correlated with reduced symptom severity. Recent infection boosted the titre and magnitude of haemagglutinin-, neuraminidase- and nucleoprotein-specific ADCC antibodies. Limited T-cell samples precluded conclusions on the role of pre- existing T-cell responses.
Conclusions. Overall, ADCC responses are a protective correlate against influenza virus infection that should be considered in future vaccine development and evaluation.Influenza-specific ADCC responses are elevated in uninfected subjects, associated with reduced symptoms and boosted by recent infection, whilst HA stem and NA IgG are also elevated in uninfected participants irrespective of ADCC function.