Overcoming Aging-Associated Poor Influenza Vaccine Responses with CpG 1018 Adjuvant.

Overcoming Aging-Associated Poor Influenza Vaccine Responses with CpG 1018 Adjuvant.
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DOI:
10.3390/vaccines10111894
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发表时间:
2022-11-10
期刊:
影响因子:
7.8
通讯作者:
Chen X
Chen X
中科院分区:
医学3区
文献类型:
--
作者:
Kang X;Li Y;Zhao Y;Chen X

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衰老与免疫系统功能下降有关,这使得老年人容易感染流感,并且对流感疫苗接种的反应也较低。这项研究探讨了CpG 1018佐剂是否有效地增强流感疫苗在相当于50多岁到60多岁早期的人类的老年小鼠中的效力。使用流感大流行2009 H1N1(pdm09)疫苗作为模型,我们发现CpG 1018佐剂可以显著增强pdm09疫苗诱导的血清抗体滴度,而单独的pdm09疫苗不能引起显著的抗体滴度。相反,单独的pdm09疫苗在年轻成年小鼠中引起显著的抗体滴度。抗体亚型分析发现,单独的pdm09疫苗在年轻的成年小鼠中引起Th2偏向的抗体应答,而CpG 1018佐剂的掺入促进了在老年小鼠中引起有效的Th1偏向的抗体应答。进一步发现,单独的pdm09疫苗诱导年轻成年小鼠中Th2细胞的显著扩增,而CpG 1018佐剂的掺入刺激老年小鼠中Th1细胞的显著扩增。CpG 1018佐剂还刺激老年小鼠中的疫苗特异性细胞毒性T淋巴细胞。在CpG 1018存在下的pdm09疫苗引起针对致命病毒攻击的显著保护,而单独的pdm09疫苗在年轻成年或老年小鼠中未能赋予显著保护。我们的研究提供了强有力的证据来支持CpG 1018佐剂在老年小鼠模型中增强流感疫苗接种的高有效性。
Aging is associated with diminished immune system function, which renders old people vulnerable to influenza infection and also less responsive to influenza vaccination. This study explored whether the CpG 1018 adjuvant was effective in enhancing influenza vaccine efficacy in aged mice equivalent to human beings in their late 50s to early 60s. Using the influenza pandemic 2009 H1N1 (pdm09) vaccine as a model, we found that the CpG 1018 adjuvant could significantly enhance the pdm09 vaccine-induced serum antibody titer, while the pdm09 vaccine alone failed to elicit significant antibody titer. In contrast, the pdm09 vaccine alone elicited significant antibody titer in young adult mice. Antibody subtype analysis found that the pdm09 vaccine alone elicited Th2-biased antibody responses in young adult mice, while incorporation of the CpG 1018 adjuvant promoted the elicitation of potent Th1-biased antibody responses in aged mice. The pdm09 vaccine alone was further found to induce significant expansion of Th2 cells in young adult mice, while incorporation of the CpG 1018 adjuvant stimulated significant expansion of Th1 cells in aged mice. The CpG 1018 adjuvant also stimulated vaccine-specific cytotoxic T lymphocytes in aged mice. The pdm09 vaccine in the presence of CpG 1018 elicited significant protection against lethal viral challenges, while the pdm09 vaccine alone failed to confer significant protection in young adult or aged mice. Our study provided strong evidence to support the high effectiveness of the CpG 1018 adjuvant to boost influenza vaccination in aged mouse models.
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