Inflammatory responses to influenza vaccination at the extremes of age

Inflammatory responses to influenza vaccination at the extremes of age
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DOI:
10.1111/imm.12742
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发表时间:
2017-08-01
期刊:
影响因子:
6.4
通讯作者:
Tregoning, John S.
Tregoning, John S.
中科院分区:
医学2区
文献类型:
--
作者:
McDonald, Jacqueline U.;Zhong, Ziyun;Tregoning, John S.

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年龄影响对疫苗接种的免疫反应,极端年龄的个体反应较差。对抗原性物质的初始炎症反应塑造了随后的适应性反应,因此需要了解年龄对急性炎症介质的影响。在这项研究中,我们测量了新生儿、青年和老年小鼠接种流感疫苗或感染后的局部和全身炎症反应。用含MF59和不含MF59佐剂的灭活流感疫苗肌肉免疫小鼠,然后用H1N1流感攻毒。年龄是影响疫苗接种后炎症特征的主要因素:新生小鼠白细胞介素-1 (IL-1)、c反应蛋白(CRP)和粒细胞-巨噬细胞集落刺激因子(GMCSF)较多,青年小鼠肿瘤坏死因子(TNF)较多,老年小鼠白细胞介素-1受体拮抗剂(IL-1RA)、IL-2RA和干扰素诱导蛋白10 (IP10)较多。值得注意的是,在所有年龄的动物中添加MF59诱导IL-5、粒细胞集落刺激因子(G-CSF)、角化细胞趋化剂(KC)和单核细胞趋化蛋白1 (MCP1),这些细胞因子的水平与抗体反应相关。年龄也对疫苗接种的效果有影响:新生儿和年轻的成年小鼠对攻击有保护作用,但老年小鼠没有。根据接触途径不同,细胞因子反应的定位存在显著差异:疫苗接种导致高血清反应,而鼻内感染导致低血清反应,但肺反应高。总之,我们证明年龄影响流感疫苗接种和感染的炎症反应。在制定针对不同年龄组的疫苗接种策略时,需要考虑到这些年龄引起的差异。
Age affects the immune response to vaccination, with individuals at the extremes of age responding poorly. The initial inflammatory response to antigenic materials shapes the subsequent adaptive response and so understanding is required about the effect of age on the profile of acute inflammatory mediators. In this study we measured the local and systemic inflammatory response after influenza vaccination or infection in neonatal, young adult and aged mice. Mice were immunized intramuscularly with inactivated influenza vaccine with and without the adjuvant MF59 and then challenged with H1N1 influenza. Age was the major factor affecting the inflammatory profile after vaccination: neonatal mice had more interleukin-1 (IL-1), C-reactive protein (CRP) and granulocyte-macrophage colony-stimulating factor (GMCSF), young adults more tumour necrosis factor- (TNF), and elderly mice more interleukin-1 receptor antagonist (IL-1RA), IL-2RA and interferon--induced protein 10 (IP10). Notably the addition of MF59 induced IL-5, granulocyte colony-stimulating factor (G-CSF), Keratinocyte Chemotractant (KC) and monocyte chemoattractant protein 1 (MCP1) in all ages of animals and levels of these cytokines correlated with antibody responses. Age also had an impact on the efficacy of vaccination: neonatal and young adult mice were protected against challenge, but aged mice were not. There were striking differences in the localization of the cytokine response depending on the route of exposure: vaccination led to a high serum response whereas intranasal infection led to a low serum response but a high lung response. In conclusion, we demonstrate that age affects the inflammatory response to both influenza vaccination and infection. These age-induced differences need to be considered when developing vaccination strategies for different age groups.