Tracking antibody profiles for influenza exposures across the lifespan

July 23, 2020

Immune responses to influenza exposures increase early in life, then decline in middle age, according to a study published July 23 in the open-access journal PLOS Pathogens by Bingyi Yang of the University of Florida, Steven Riley of Imperial College London, Derek Cummings of the University of Florida, and colleagues. Using novel metrics defining the key characteristics of antibody profiles, the researchers showed that influenza exposures over the lifetime continually shape antibody profiles, which drive future immune responses to influenza.

Seasonal influenza remains a ubiquitous threat to human health. Each infection leaves a mark on a person's immune system, and the accumulation of antibody responses over a lifetime leads to complex individual antibody profiles reflecting past exposures. A growing body of evidence suggests that the order and timing of influenza exposures shape the immune response in ways that may affect morbidity and mortality, particularly when encountering novel (i.e., pandemic or potentially pandemic) strains. But it has not been clear how past exposures to multiple strains vary across individuals and time and determine future infection risk and subsequent immune responses. To address this gap in knowledge, the researchers developed several novel metrics to define the key features of antibody profiles.

Specifically, they characterized antibody profiles at two time points (baseline from 2009 to 2011 and follow-up from 2014 to 2015), roughly four years apart, in a large sample of individuals, aged 2 to 86, in Guangzhou, Guangdong Province, China. They measured immune responses to 21 H3N2 influenza strains that represent the history of H3N2 circulation in humans since its emergence in 1968. Using these metrics, they found that immunity accumulates during the first twenty years of life and then declines until 40 to 50 years of age. These age patterns in antibody profiles are likely driven by continual exposure to influenza and the effects of existing immunity on immune responses to newly encountered strains. In addition, individuals with higher immunity to older, previously exposed strains show increased antibody production to recent strains. According to the authors, this study provides quantitative tools to analyze complex antibody profiles and to improve the understanding of heterogeneity in antibody responses and vaccine efficacy across age groups.

"We found antibody profiles to provide more information than homologous titers in predicting temporal changes in influenza immunity," the authors conclude.
Research Article

Funding: This study was supported by grants from the NIH R56AG048075 (D.A.T.C., J.L.), NIH R01AI114703 (D.A.T.C., B.Y.), the Wellcome Trust 200861/Z/16/Z (S.R.) and 200187/Z/15/Z (S.R.). D.A.T.C., J.M.R. and S.R. acknowledge support from the National Institutes of Health Fogarty Institute (R01TW0008246). J.M.R. acknowledges support from the Medical Research Council (MR/S004793/1) and the Engineering and Physical Sciences Research Council (EP/N014499/1). S.R. acknowledges National Institute for Health Research (UK, for Health Protection Research Unit funding). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation: Yang B, Lessler J, Zhu H, Jiang CQ, Read JM, Hay JA, et al. (2020) Life course exposures continually shape antibody profiles and risk of seroconversion to influenza. PLoS Pathog 16(7): e1008635.

Author Affiliations:

Department of Biology, University of Florida, Gainesville, Florida, United States of America

Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America

State Key Laboratory of Emerging Infectious Diseases and Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong SAR, China

Joint Institute of Virology (Shantou University-The University of Hong Kong), Shantou University, Shantou, Guangdong, China

Guangzhou No.12 Hospital, Guangzhou, Guangdong, China

Centre for Health Informatics Computing and Statistics, Lancaster Medical School, Lancaster University, Lancaster, United Kingdom

MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom

The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China

Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, China

Shenzhen Research Institute of The Chinese University of Hong Kong, Shenzhen, Guangdong, China

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