College of Animal Science and Technology, Jilin Provincial Engineering Research Center of Animal Probiotics, Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, 130118, China.
Sci Rep. 2016 Dec 22;6:39665. doi: 10.1038/srep39665.
Avian influenza virus (AIV) can infect birds and mammals, including humans, and are thus a serious threat to public health. Vaccination is vital for controlling AIV circulation. In this study, we generated a recombinant lactobacillus expressing the NP-M1-DCpep of H9N2 avian influenza virus and evaluated the activation effect of NC8-pSIP409-NP-M1-DCpep on dendritic cells (DCs) in a mouse model. The specific mucosal antibody responses and B and T cell responses in lymphoid tissues were also characterized. Importantly, we confirmed that specific CD8 T cells presented in vitro and antigen-specific cytotoxicity (activated the expression of CD107a) and in vivo antigen-specific cytotoxicity after vaccination. The adoptive transfer of NC8-pSIP409-NP-M1-DCpep-primed CD8 T cells into NOD-SCID mice resulted in effective protection against mouse-adapted AIV infection. In addition, we observed protection in immunized mice challenged with mouse-adapted H9N2 AIV and H1N1 influenza virus, as evidenced by reductions in the lung virus titers, improvements in lung pathology, and weight loss and complete survival. Our data are promising for the generation of effective, non-traditional influenza vaccines against AIVs.
禽流感病毒(AIV)可以感染鸟类和哺乳动物,包括人类,因此对公共卫生构成严重威胁。疫苗接种对于控制 AIV 的传播至关重要。在这项研究中,我们构建了一种表达 H9N2 禽流感病毒 NP-M1-DCpep 的重组乳酸杆菌,并在小鼠模型中评估了 NC8-pSIP409-NP-M1-DCpep 对树突状细胞(DC)的激活作用。还对淋巴组织中的特异性黏膜抗体反应和 B 和 T 细胞反应进行了表征。重要的是,我们证实了特异性 CD8 T 细胞在体外和接种后的体内抗原特异性细胞毒性(激活 CD107a 的表达)中呈现。将 NC8-pSIP409-NP-M1-DCpep 诱导的 CD8 T 细胞过继转移到 NOD-SCID 小鼠中,可有效预防小鼠适应的 AIV 感染。此外,我们观察到免疫接种的小鼠对小鼠适应的 H9N2 AIV 和 H1N1 流感病毒的保护作用,这表现在肺病毒滴度降低、肺病理改善、体重减轻和完全存活。我们的数据为开发针对 AIV 的有效、非传统流感疫苗提供了有希望的结果。