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聚乙二醛佐剂流感 A(H7N9)抗原 HA1-2 在鸡中诱导增强的 Th1/Th2 混合免疫应答。

Enhanced Th1/Th2 mixed immune responses elicited by polyethyleneimine adjuvanted influenza A (H7N9) antigen HA1-2 in chickens.

机构信息

Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225009, China.

Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China.

出版信息

Poult Sci. 2018 Dec 1;97(12):4245-4251. doi: 10.3382/ps/pey313.

DOI:10.3382/ps/pey313
PMID:30085299
Abstract

Influenza A (H7N9) viruses have caused severe human infections and deaths every year in China since 2013. To reduce the risk of human infection and prevent a new influenza pandemic, there is a pressing need to develop safe and effective anti-H7N9 vaccines for poultry. Polyethyleneimine (PEI) is an organic polycation used extensively as a transfection reagent for decades. Although the adjuvant potential of PEI is well studied in mammals, its applicability and immune characteristics to avian species are still very rare. Here, to investigate the adjuvant activity of PEI, we analyzed the immune responses in chicken peripheral blood mononuclear cells in vitro. PEI significantly upregulated the expression of immune-related cytokines (IFN-γ, IL-2, IL-4, IL-6, IL-18, and IL-1β) and chemokines (CXCLi1, CXCLi2, MIP-1β, and MCP-3), suggesting that PEI promoted immune responses of avian cells. We also assessed the in vivo immune responses to PEI in a chicken model. After the second and third vaccinations, significantly higher IgG titers were observed in the chickens immunized with HA1-2+PEI than that of HA1-2 alone. The HA1-2+PEI group also increased percentages of CD4+ and CD8+ T cells and improved PBMC proliferation. The significantly upregulated IFN-γ and IL-4 levels of splenocytes from HA1-2+PEI vaccinated chickens further indicated that PEI promoted a Th1/Th2 mixed immune responses. This study not only demonstrates the adjuvant potential of PEI when co-administered with influenza H7N9 antigen HA1-2 in chickens, but also supports the use of PEI as a versatile systemic adjuvant platform in poultry.

摘要

自 2013 年以来,甲型流感(H7N9)病毒每年在中国导致严重的人类感染和死亡。为了降低人类感染的风险并预防新的流感大流行,迫切需要为家禽开发安全有效的抗 H7N9 疫苗。聚乙烯亚胺(PEI)是一种有机聚阳离子,几十年来一直被广泛用作转染试剂。尽管 PEI 的佐剂潜力在哺乳动物中得到了很好的研究,但它在禽类中的适用性和免疫特性仍然很少见。在这里,为了研究 PEI 的佐剂活性,我们分析了鸡外周血单核细胞在体外的免疫反应。PEI 显著上调了免疫相关细胞因子(IFN-γ、IL-2、IL-4、IL-6、IL-18 和 IL-1β)和趋化因子(CXCLi1、CXCLi2、MIP-1β 和 MCP-3)的表达,表明 PEI 促进了禽类细胞的免疫反应。我们还评估了 PEI 在鸡模型中的体内免疫反应。在第二次和第三次接种后,与单独接种 HA1-2 相比,在接种 HA1-2+PEI 的鸡中观察到 IgG 滴度显著升高。HA1-2+PEI 组还增加了 CD4+和 CD8+T 细胞的百分比,并改善了 PBMC 增殖。来自 HA1-2+PEI 免疫鸡的脾细胞中 IFN-γ和 IL-4 水平的显著上调进一步表明,PEI 促进了 Th1/Th2 混合免疫反应。这项研究不仅证明了 PEI 与流感 H7N9 抗原 HA1-2 共同给药时在鸡中的佐剂潜力,还支持将 PEI 用作家禽的多功能系统佐剂平台。

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