黄芪多糖可提高流感疫苗的免疫原性，并调节 BALB/c 小鼠的肠道微生物群。
Astragalus Polysaccharide improves immunogenicity of influenza vaccine as well as modulate gut microbiota in BALB/c mice.
机构信息
Department of Emergency, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, Xuhui, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
出版信息
Microb Pathog. 2024 Oct;195:106893. doi: 10.1016/j.micpath.2024.106893. Epub 2024 Aug 27.
BACKGROUND
Vaccination is the best way to prevent influenza virus infection, and insufficient antibodies make it difficult to resist influenza virus invasion. Astragalus Polysaccharide (APS) has a boosting effect on immunity, so we evaluate the effect of APS as an immune adjuvant for H1N1 influenza vaccines in this study.
METHODS
The mice were immunized twice with influenza A (H1N1) vaccine and APS. Subsequently, the serum antibody levels were assessed using enzyme-linked immunosorbent assay (ELISA). The frequency of peripheral immune T cells was determined by flow cytometry. Following this, the immunized mice were exposed to a lethal dose of the virus, and changes in body weight and survival rates were recorded. Hematoxylin-eosin staining was employed to observe pathological alterations in lung and intestinal tissues. Western blot analysis was conducted to detect the expression of intestinal barrier function proteins (Occludin and Claudin-1). ELISA was utilized to measure the expression level of serum inflammatory cytokine TNF-α. Fresh mouse feces were collected after the initial immunization as well as after viral infection for 16S rRNA analysis aimed at detecting alterations in gut microbiota.
RESULTS
Compared to the Hemagglutinin (HA) group, the APS group demonstrated higher levels of immunoglobulin G (IgG), IgG1, and IgG3, as well as neutralizing antibody levels. Additionally, it increased the frequency of CD8 cells to enhance resistance against lethal infection. On day 14 post-infection, the high-dose APS group exhibited a higher survival rate (71.40 %) compared to the HA group (14.28 %), along with faster weight recovery. Furthermore, APS was found to ameliorate alveolar damage in lung tissue and rectify intestinal structural disorder. It also upregulated the expression levels of tight junction proteins Occludin and Claudin-1 in intestinal tissue while reducing serum TNF-α expression levels. In addition, populations of Colidextribacter, Peptococcaceae, and Ruminococcaceae were the dominant gut microbiota in the APS group after viral infection.
CONCLUSION
APS has an immune-enhancing effect and is expected to be a novel adjuvant in the H1N1 influenza vaccine.
背景
接种疫苗是预防流感病毒感染的最佳方法，而抗体不足则难以抵抗流感病毒的侵袭。黄芪多糖（APS）对免疫具有增强作用，因此我们在这项研究中评估了 APS 作为 H1N1 流感疫苗免疫佐剂的效果。
方法
用流感 A（H1N1）疫苗和 APS 对小鼠进行两次免疫。随后，通过酶联免疫吸附试验（ELISA）评估血清抗体水平。用流式细胞术测定外周免疫 T 细胞的频率。之后，用致死剂量的病毒感染免疫小鼠，记录体重变化和存活率。用苏木精-伊红染色观察肺和肠道组织的病理变化。用 Western blot 分析检测肠道屏障功能蛋白（Occludin 和 Claudin-1）的表达。用 ELISA 测定血清炎症细胞因子 TNF-α的表达水平。在初次免疫后和病毒感染后 16S rRNA 分析时收集新鲜的小鼠粪便，以检测肠道微生物群的变化。
结果
与血凝素（HA）组相比，APS 组的免疫球蛋白 G（IgG）、IgG1 和 IgG3 以及中和抗体水平更高。此外，它增加了 CD8 细胞的频率，增强了对致死性感染的抵抗力。感染后第 14 天，高剂量 APS 组的存活率（71.40%）高于 HA 组（14.28%），且体重恢复较快。此外，APS 改善了肺组织肺泡损伤，纠正了肠道结构紊乱。它还上调了肠道组织中紧密连接蛋白 Occludin 和 Claudin-1 的表达水平，同时降低了血清 TNF-α的表达水平。此外，感染后病毒，Colidextribacter、Peptococcaceae 和 Ruminococcaceae 是 APS 组中的优势肠道菌群。
结论
APS 具有免疫增强作用，有望成为 H1N1 流感疫苗的新型佐剂。
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