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

Jia, JZ and Cohen, CA and Gu, H and McLean, MR and Varadarajan, R and Bhandari, N and Peiris, M and Leung, GM and Poon, LLM and Tsang, T and Chung, AW and Cowling, BJ and Leung, NHL and Valkenburg, SA (2024) Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children. In: Nature Communications, 15 (1).

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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�. © The Author(s) 2024.

Item Type:	Journal Article
Publication:	Nature Communications
Publisher:	Nature Research
Additional Information:	The copyright for this article belongs to authors.
Keywords:	antibody; antigen; antiserum; cross reacting antibody; Fc receptor; hemagglutinin; immunoglobulin G; immunoglobulin G1; immunoglobulin G1 antibody; immunoglobulin G3; immunoglobulin M; influenza vaccine; neutralizing antibody; placebo; influenza vaccine; neutralizing antibody; virus antibody, antibody; child health; immune response; influenza; inhibition; serum; vaccination, 2009 H1N1 influenza; antibody dependent cellular cytotoxicity; antibody response; antibody specificity; antigen binding; Article; binding assay; biobank; biotinylation; cell assay; cell function; child; controlled study; cross reaction; cross validation; degranulation; elastic tissue; factor analysis; false negative result; false positive result; feature selection; female; fluorescence activated cell sorting; hemagglutination; human; immune response; infection sensitivity; influenza; influenza vaccination; male; natural killer cell; network analysis; NK-92 cell line; pandemic; parameters; positivity rate; prediction; predictive model; principal component analysis; protein expression; randomized controlled trial (topic); real time polymerase chain reaction; sampling; school child; seroconversion; Severe acute respiratory syndrome coronavirus 2; virus load; influenza; Influenza A virus (H1N1); prospective study; randomized controlled trial, Antibodies, Neutralizing; Antibodies, Viral; Child; Humans; Immunoglobulin G; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Influenza, Human; Prospective Studies
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	17 May 2024 05:17
Last Modified:	29 Nov 2024 09:32
URI:	http://eprints.iisc.ac.in/id/eprint/84723

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