Evidence for antigenic seniority in influenza A (H3N2) antibody responses in southern China.
Evidence for antigenic seniority in influenza A (H3N2) antibody responses in southern China.
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DOI：
10.1371/journal.ppat.1002802
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发表时间：
2012
期刊：
影响因子：
6.7
通讯作者：
Cummings DA
中科院分区：
文献类型：
--
作者：
Lessler J;Riley S;Read JM;Wang S;Zhu H;Smith GJ;Guan Y;Jiang CQ;Cummings DA
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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. The human immune response to an influenza infection is not the same for every infection. It has often been observed that we tend to have the highest antibody titer (and presumably our strongest immune response) against strains of influenza that we were exposed to early in life. In this study, we obtained blood samples from 151 people between 7 and 81 years of age and tested the samples for the concentration of antibodies to many different (H3N2) strains. We chose strains according to when they first circulated, starting with a strain isolated just after the 1968 pandemic and going all the way through to very recent strains. We found that a participant's age at the time a strain first circulated was very predictive of the strength of their antibody against that strain. Not just for the first strain they were likely to have seen, but also for the second, third and all subsequent strains circulating during their lifetime. This suggests to us that antibody titers to influenza A H3N2 follow a pattern of antigenic seniority, suggesting that we produce progressively fewer specific antibodies to each subsequent infection as we age.
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