Immuno-epidemiologic Correlates of Pandemic H1N1 Surveillance Observations: Higher Antibody and Lower Cell-Mediated Immune Responses with Advanced Age
Immuno-epidemiologic Correlates of Pandemic H1N1 Surveillance Observations: Higher Antibody and Lower Cell-Mediated Immune Responses with Advanced Age
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DOI：
10.1093/infdis/jiq039
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发表时间：
2011-01-15
影响因子：
6.4
通讯作者：
Petric, Martin
中科院分区：
文献类型：
--
作者：
Skowronski, Danuta M.;Hottes, Travis S.;Petric, Martin
背景。 H1N1 流感大流行 (pH1N1) 监测数据显示，随着年龄的增长，发病率较低，但发生严重后果的风险较高。我们探讨了监测结果的免疫流行病学相关性，包括体液免疫和细胞介导的免疫（CMI）。方法。在基于年龄的设计中，通过血凝抑制 (HI) 和微量中和 (MN) 测定对每个 10 岁年龄层的 100 份储存/残留血清进行评估，以评估预先存在的 pH1N1 抗体以及最近的季节性 H1N1 和 H3N2 菌株。在由儿童甲型流感/亚型引发（1919-1929：H1N1；1945-1949：H1N1；1958-1960：H2N2；1969-1970：H3N2；1978-1989：H3N2/H1N1）定义的单独出生队列设计中，每次出生从最多 50 名志愿者中采集全血队列。体外评估Th1（IFN-γ）：Th2（IL-10）细胞因子反应的比率。结果。学龄儿童的季节性病毒抗体最高。参与者中对 pH1N1 的交叉反应性 HI/MN 抗体较低 = 40)，但血清阳性率在 70-79 岁 (27%/6%) 时增加，在 80-89 岁 (65%/47%) 时增加更多，并且在 >= 90 岁 (88%/76%) 时最高。 CMI 至 pH1N1 在所有 5 个出生队列中都很明显，但与季节性菌株相比较低。亚型引发几乎没有差异，但所有病毒的 Th1:Th2 比率在 2 个最古老的队列中显着下降。结论。先前存在的抗体可能可以保护老年人免受 pH1N1 感染，而 CMI 的减弱可能会导致感染后病情更加严重。在年轻人中，交叉反应性 pH1N1 抗体大多不存在，而更完整的 CMI 可能可以防止出现严重后果。
Background. Pandemic H1N1 (pH1N1) surveillance data showed lower attack rates but higher risk of severe outcomes with advanced age. We explored immuno-epidemiologic correlates of surveillance findings including humoral and cell-mediated immunity (CMI).Methods. In an age-based design, similar to 100 banked/residual sera per 10-year age stratum were assessed by hemagglutination inhibition (HI) and microneutralization (MN) assays for preexisting antibody to pH1N1 and recent seasonal H1N1 and H3N2 strains. In a separate birth cohort design defined by childhood influenza A/subtype priming (1919-1929: H1N1; 1945-1949: H1N1; 1958-1960: H2N2; 1969-1970: H3N2; 1978-1989: H3N2/H1N1), whole blood was collected from up to 50 volunteers per birth cohort. The ratio of Th1(IFN-gamma):Th2(IL-10) cytokine responses was evaluated in vitro.Results. Antibody to seasonal viruses was highest in school-age children. Cross-reactive HI/MN antibody to pH1N1 was low among participants = 40), but seroprevalence increased at 70-79 yoa (27%/6%), increased even more at 80-89 yoa (65%/47%), and was highest at >= 90 yoa (88%/76%). CMI to pH1N1 was evident in all 5 birth cohorts but was lower compared with seasonal strains. There was little differentiation by subtype priming, but the Th1:Th2 ratio for all viruses dropped significantly in the 2 oldest cohorts.Conclusions. Preexisting antibody may have protected the very old from pH1N1 infection, while diminished CMI may have contributed to greater severity once infected. In the young, cross-reactive pH1N1 antibody was mostly absent, while more intact CMI may have protected against severe outcomes.