Immunology Division, Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, 6020 Innsbruck, Austria.
Vaccine. 2011 May 23;29(23):3982-9. doi: 10.1016/j.vaccine.2011.03.081. Epub 2011 Apr 8.
Streptococcus pneumoniae is a major human pathogen, causing high morbidity and mortality in children, and also in the elderly, who are particularly susceptible to S. pneumoniae infections due to the dysregulated function of the aged immune system. As the current generation of polysaccharide vaccines do not provide sufficient protection for elderly, new vaccination strategies are urgently needed. To learn whether pneumococcal proteins are able to induce adaptive immune responses in adults in different age groups, we determined serum IgG antibody titers and T cell immunity (IFN-γ, IL-17A and IL-5 production) to three pneumococcal antigens, PcsB, StkP and PsaA, that are components of an investigational protein-based pneumococcal vaccine, IC47. Therefore, sera and PBMCs of 108 healthy adults in three different age groups (young, middle-aged and elderly) were analyzed by ELISA and ELISpot, respectively. We found naturally acquired antibodies to all three proteins in all age groups against all three antigens. However, elderly individuals had significantly lower IgG levels to PcsB and PsaA compared to those of younger donors. There was no significant age-related difference in the overall rate of T cell immunity for the three pneumococcal proteins. We found that the Th17 response was dominant in all age groups and was frequently combined with a Th1 or Th2 response in young and middle-aged subjects. However, in elderly persons there was a lower percentage of PBMC samples producing more than one cytokine upon antigenic stimulation. The narrow cytokine secretion pattern was the most striking difference between elderly and younger adult age groups. Our results demonstrate that in the majority of adults there is a naturally acquired humoral and cellular immune response to the three pneumococcal proteins tested. The dominance of the Th17 response is especially interesting in the light of new insights regarding the role of Th17 cells in mucosal protection against this pathogen.
肺炎链球菌是一种主要的人类病原体，可导致儿童和老年人发病率和死亡率升高，由于衰老免疫系统功能失调，老年人特别容易受到肺炎链球菌感染。由于当前一代多糖疫苗不能为老年人提供充分的保护，因此迫切需要新的疫苗接种策略。为了了解肺炎链球菌蛋白是否能够在不同年龄组的成年人中诱导适应性免疫反应，我们测定了三种肺炎链球菌抗原（PcsB、StkP 和 PsaA）的血清 IgG 抗体滴度和 T 细胞免疫（IFN-γ、IL-17A 和 IL-5 产生），这些抗原是一种研究性蛋白基肺炎球菌疫苗 IC47 的组成部分。因此，我们通过 ELISA 和 ELISpot 分析了来自三个不同年龄组（年轻、中年和老年）的 108 名健康成年人的血清和 PBMC。我们发现，所有年龄组的个体对所有三种抗原都存在针对这三种蛋白的天然获得性抗体。然而，与年轻供体相比，老年人对 PcsB 和 PsaA 的 IgG 水平显著降低。对于三种肺炎链球菌蛋白，T 细胞免疫的总体率与年龄无关。我们发现，所有年龄组均以 Th17 反应为主，在年轻和中年个体中，该反应常与 Th1 或 Th2 反应相结合。然而，在老年人中，抗原刺激后产生多于一种细胞因子的 PBMC 样本的比例较低。这种狭窄的细胞因子分泌模式是老年人和年轻成年人群体之间最显著的差异。我们的研究结果表明，在大多数成年人中，存在针对三种测试的肺炎链球菌蛋白的天然获得性体液和细胞免疫反应。Th17 反应的优势尤其有趣，因为它为 Th17 细胞在针对这种病原体的粘膜保护中的作用提供了新的见解。
