McDonald Jacqueline U, Zhong Ziyun, Groves Helen T, Tregoning John S
Mucosal Infection and Immunity group, Section of Virology, Department of Medicine, Imperial College London, London, UK.
Immunology. 2017 Aug;151(4):451-463. doi: 10.1111/imm.12742. Epub 2017 May 16.
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-1α (IL-1α), C-reactive protein (CRP) and granulocyte-macrophage colony-stimulating factor (GMCSF), young adults more tumour necrosis factor-α (TNF), and elderly mice more interleukin-1 receptor antagonist (IL-1RA), IL-2RA and interferon-γ-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.
年龄会影响对疫苗接种的免疫反应，年龄两端的个体反应较差。对抗抗原物质的初始炎症反应会塑造随后的适应性反应，因此需要了解年龄对急性炎症介质谱的影响。在本研究中，我们测量了新生、年轻成年和老年小鼠接种流感疫苗或感染流感后的局部和全身炎症反应。小鼠通过肌肉注射接种含或不含佐剂MF59的灭活流感疫苗，然后用H1N1流感病毒进行攻击。年龄是影响接种疫苗后炎症谱的主要因素：新生小鼠的白细胞介素-1α（IL-1α）、C反应蛋白（CRP）和粒细胞-巨噬细胞集落刺激因子（GMCSF）更多，年轻成年小鼠的肿瘤坏死因子-α（TNF）更多，老年小鼠的白细胞介素-1受体拮抗剂（IL-1RA）、IL-2RA和干扰素-γ诱导蛋白10（IP10）更多。值得注意的是，添加MF59可在所有年龄段的动物中诱导IL-5、粒细胞集落刺激因子（G-CSF）、角质形成细胞趋化因子（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。年龄也对接种疫苗的效果有影响：新生和年轻成年小鼠受到保护免受攻击，但老年小鼠则不然。根据暴露途径的不同，细胞因子反应的定位存在显著差异：接种疫苗导致血清反应高，而鼻内感染导致血清反应低但肺部反应高。总之，我们证明年龄会影响对流感疫苗接种和感染的炎症反应。在为不同年龄组制定疫苗接种策略时，需要考虑这些由年龄引起的差异。
