PDF(Pubmed)
Abstract：
Nonhuman adenoviral (AdV) gene delivery platforms have significant value due to their ability to elude preexisting AdV vector immunity in most individuals. Previously, we have demonstrated that intranasal (IN) immunization of mice with BAd-H5HA, a bovine AdV type 3 (BAdV3) vector expressing H5N1 influenza virus hemagglutinin (HA), resulted in enhanced humoral and cell-mediated immune responses. The BAd-H5HA IN immunization resulted in complete protection following the challenge with an antigenically distinct H5N1 virus compared to the mouse group similarly immunized with HAd-H5HA, a human AdV type 5 (HAdV5) vector expressing HA.
Here, we attempted to determine the activation of innate immune responses in the lungs of mice inoculated intranasally with BAd-H5HA compared to the HAd-H5HA-inoculated group.
RNA-Seq analyses of the lung tissues revealed differential expression (DE) of genes involved in innate and adaptive immunity in animals immunized with BAd-H5HA. The top ten enhanced genes were verified by RT-PCR. Consistently, there were transient increases in the levels of cytokines (IL-1α, IL-1β, IL-5, TNF- α, LIF, IL-17, G-CSF, MIP-1β, MCP-1, MIP-2, and GM-CSF) and toll-like receptors in the lungs of the group inoculated with BAdV vectors compared to that of the HAdV vector group.
These results demonstrate that the BAdV vectors induce enhanced innate and adaptive immunity-related factors compared to HAdV vectors in mice. Thus, the BAdV vector platform could be an excellent gene delivery system for recombinant vaccines and cancer immunotherapy.
Here, we attempted to determine the activation of innate immune responses in the lungs of mice inoculated intranasally with BAd-H5HA compared to the HAd-H5HA-inoculated group.
RNA-Seq analyses of the lung tissues revealed differential expression (DE) of genes involved in innate and adaptive immunity in animals immunized with BAd-H5HA. The top ten enhanced genes were verified by RT-PCR. Consistently, there were transient increases in the levels of cytokines (IL-1α, IL-1β, IL-5, TNF- α, LIF, IL-17, G-CSF, MIP-1β, MCP-1, MIP-2, and GM-CSF) and toll-like receptors in the lungs of the group inoculated with BAdV vectors compared to that of the HAdV vector group.
These results demonstrate that the BAdV vectors induce enhanced innate and adaptive immunity-related factors compared to HAdV vectors in mice. Thus, the BAdV vector platform could be an excellent gene delivery system for recombinant vaccines and cancer immunotherapy.
摘要：
■非人腺病毒(AdV)基因递送平台由于其在大多数个体中逃避预先存在的AdV载体免疫的能力而具有显著的价值。以前,我们已经证明，用BAd-H5HA鼻内（IN）免疫小鼠，表达H5N1流感病毒血凝素（HA）的牛AdV3型（BAdV3）载体，导致增强的体液和细胞介导的免疫反应。与用HAd-H5HA类似免疫的小鼠组相比，用抗原性不同的H5N1病毒攻击后，Bad-H5HAIN免疫导致完全保护。表达HA的人AdV5型(HAdV5)载体。
■这里，我们试图确定与HAd-H5HA接种组相比,鼻内接种BAd-H5HA的小鼠肺中先天免疫应答的激活。
■肺组织的RNA-Seq分析揭示了在用BAd-H5HA免疫的动物中参与先天和适应性免疫的基因的差异表达(DE)。通过RT-PCR验证前10个增强基因。始终如一，细胞因子(IL-1α，IL-1β,IL-5，TNF-α，LIF,IL-17,G-CSF,MIP-1β,与HAdV载体组相比，接种BAdV载体组的肺中的MCP-1，MIP-2和GM-CSF）和toll样受体。
■这些结果表明，与HAdV载体相比，BAdV载体在小鼠中诱导增强的先天和适应性免疫相关因子。因此，BAdV载体平台可能是重组疫苗和癌症免疫治疗的优良基因传递系统。
■这里，我们试图确定与HAd-H5HA接种组相比,鼻内接种BAd-H5HA的小鼠肺中先天免疫应答的激活。
■肺组织的RNA-Seq分析揭示了在用BAd-H5HA免疫的动物中参与先天和适应性免疫的基因的差异表达(DE)。通过RT-PCR验证前10个增强基因。始终如一，细胞因子(IL-1α，IL-1β,IL-5，TNF-α，LIF,IL-17,G-CSF,MIP-1β,与HAdV载体组相比，接种BAdV载体组的肺中的MCP-1，MIP-2和GM-CSF）和toll样受体。
■这些结果表明，与HAdV载体相比，BAdV载体在小鼠中诱导增强的先天和适应性免疫相关因子。因此，BAdV载体平台可能是重组疫苗和癌症免疫治疗的优良基因传递系统。
