Title Evidence for antigenic seniority in influenza A ( H 3 N 2 ) antibodyresponses in southern China

A key observation about the human immune response to repeated exposure to influenza A is that the first strain infecting an individual apparently produces the strongest adaptive immune response. Although antibody titers measure that response, the interpretation of titers to multiple strains – from the same sera – in terms of infection history is clouded by age effects, cross reactivity and immune waning. From July to September 2009, we collected serum samples from 151 residents of Guangdong Province, China, 7 to 81 years of age. Neutralization tests were performed against strains representing six antigenic clusters of H3N2 influenza circulating between 1968 and 2008, and three recent locally circulating strains. Patterns of neutralization titers were compared based on age at time of testing and age at time of the first isolation of each virus. Neutralization titers were highest for H3N2 strains that circulated in an individual’s first decade of life (peaking at 7 years). Further, across strains and ages at testing, statistical models strongly supported a pattern of titers declining smoothly with age at the time a strain was first isolated. Those born 10 or more years after a strain emerged generally had undetectable neutralization titers to that strain (,1:10). Among those over 60 at time of testing, titers tended to increase with age. The observed pattern in H3N2 neutralization titers can be characterized as one of antigenic seniority: repeated exposure and the immune response combine to produce antibody titers that are higher to more ‘senior’ strains encountered earlier in life. Citation: Lessler J, Riley S, Read JM, Wang S, Zhu H, et al. (2012) Evidence for Antigenic Seniority in Influenza A (H3N2) Antibody Responses in Southern China. PLoS Pathog 8(7): e1002802. doi:10.1371/journal.ppat.1002802 Editor: Christopher F. Basler, Mount Sinai School of Medicine, United States of America Received September 11, 2011; Accepted June 1, 2012; Published July 19, 2012 Copyright: 2012 Lessler et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was supported by: a grant from the National Institutes of Health Fogarty Institute (1 R01 TW 0008246-01); the RAPIDD program from Fogarty International Centre with the Science & Technology Directorate, Department of Homeland Security (SR, DATC); Career Award at the Scientific Interface from the Burroughs Wellcome Fund (DATC); and Wellcome Trust University Award 093488/Z/10/Z (SR). 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. * E-mail: s.riley@imperial.ac.uk