Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children

Janice Z. Jia, Carolyn A. Cohen, Haogao Gu, Milla R. McLean, Raghavan Varadarajan, Nisha Bhandari, Malik Peiris, Gabriel M. Leung, Leo L. M. Poon, Tim Tsang, Amy W. Chung, Benjamin J. Cowling, Nancy H. L. Leung and Sophie A. Valkenburg ()
Additional contact information
Janice Z. Jia: The University of Hong Kong
Carolyn A. Cohen: The University of Hong Kong
Haogao Gu: The University of Hong Kong
Milla R. McLean: University of Melbourne
Raghavan Varadarajan: Indian Institute of Science
Nisha Bhandari: Indian Institute of Science
Malik Peiris: The University of Hong Kong
Gabriel M. Leung: The University of Hong Kong
Leo L. M. Poon: The University of Hong Kong
Tim Tsang: The University of Hong Kong
Amy W. Chung: University of Melbourne
Benjamin J. Cowling: The University of Hong Kong
Nancy H. L. Leung: The University of Hong Kong
Sophie A. Valkenburg: The University of Hong Kong

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Cross-reactive antibodies with Fc receptor (FcR) effector functions may mitigate pandemic virus impact in the absence of neutralizing antibodies. In this exploratory study, we use serum from a randomized placebo-controlled trial of seasonal trivalent influenza vaccination in children (NCT00792051) conducted at the onset of the 2009 H1N1 pandemic (pH1N1) and monitored for infection. We found that seasonal vaccination increases pH1N1 specific antibodies and FcR effector functions. Furthermore, prospective baseline antibody profiles after seasonal vaccination, prior to pH1N1 infection, show that unvaccinated uninfected children have elevated ADCC effector function, FcγR3a and FcγR2a binding antibodies to multiple pH1N1 proteins, past seasonal and avian (H5, H7 and H9) strains. Whereas, children that became pH1N1 infected after seasonal vaccination have antibodies focussed to seasonal strains without FcR functions, and greater aggregated HA-specific profiles for IgM and IgG3. Modeling to predict infection susceptibility, ranked baseline hemagglutination antibody inhibition as the highest contributor to lack of pH1N1 infection, in combination with features that include pH1-IgG1, H1-stem responses and FcR binding to seasonal vaccine and pH1 proteins. Thus, seasonal vaccination can have benefits against pandemic influenza viruses, and some children already have broadly reactive antibodies with Fc potential without vaccination and may be considered ‘elite influenza controllers’.

Date: 2024
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DOI: 10.1038/s41467-024-47590-0

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