Kang Xinliang, Li Yibo, Zhao Yiwen, Chen Xinyuan
Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Pharmacy Building, Room 480, Kingston, RI 02881, USA.
Vaccines (Basel). 2022 Nov 10;10(11):1894. doi: 10.3390/vaccines10111894.
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.
衰老与免疫系统功能衰退有关，这使得老年人易受流感感染，且对流感疫苗的反应也较弱。本研究探讨了CpG 1018佐剂是否能有效增强在年龄上相当于人类50多岁至60岁出头的老年小鼠体内的流感疫苗效力。以2009年甲型H1N1流感大流行（pdm09）疫苗为模型，我们发现CpG 1018佐剂可显著提高pdm09疫苗诱导的血清抗体滴度，而单独使用pdm09疫苗未能引发显著的抗体滴度。相比之下，单独使用pdm09疫苗能在年轻成年小鼠中引发显著的抗体滴度。抗体亚型分析发现，单独使用pdm09疫苗在年轻成年小鼠中引发了以Th2为主的抗体反应，而加入CpG 1018佐剂则促进了老年小鼠中强效的以Th1为主的抗体反应的产生。进一步发现，单独使用pdm09疫苗可诱导年轻成年小鼠中Th2细胞显著扩增，而加入CpG 1018佐剂则刺激老年小鼠中Th1细胞显著扩增。CpG 1018佐剂还刺激了老年小鼠中的疫苗特异性细胞毒性T淋巴细胞。在CpG 1018存在的情况下，pdm09疫苗对致死性病毒攻击产生了显著的保护作用，而单独使用pdm09疫苗在年轻成年或老年小鼠中均未能提供显著的保护。我们的研究提供了有力证据，支持CpG 1018佐剂在老年小鼠模型中增强流感疫苗接种效果方面具有高效性。
