Enhancement of mucosal innate and adaptive immunity following intranasal immunization of mice with a bovine adenoviral vector.

Enhancement of mucosal innate and adaptive immunity following intranasal immunization of mice with a bovine adenoviral vector.
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DOI:
10.3389/fimmu.2023.1305937
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发表时间:
2023
影响因子:
7.3
通讯作者:
Mittal, Suresh K.
Mittal, Suresh K.
中科院分区:
医学2区
文献类型:
--
作者:
Sayedahmed, Ekramy E.;Elshafie, Nelly O.;Zhang, Guangjun;Mohammed, Sulma I.;Sambhara, Suryaprakash;Mittal, Suresh K.

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非人腺病毒 (AdV) 基因传递平台具有重要价值,因为它们能够逃避大多数个体中预先存在的 AdV 载体免疫。此前,我们已经证明,用表达 H5N1 流感病毒血凝素 (HA) 的牛 AdV 3 型 (BAdV3) 载体 BAd-H5HA 对小鼠进行鼻内 (IN) 免疫,可增强体液和细胞介导的免疫反应。与用HAd-H5HA(一种表达HA的人AdV 5型(HAdV5)载体)类似免疫的小鼠组相比,BAd-H5HA IN免疫在用抗原不同的H5N1病毒攻击后产生了完全保护。在这里,我们试图确定与 HAd-H5HA 接种组相比,鼻内接种 BAd-H5HA 的小鼠肺部先天免疫反应的激活情况。肺组织的 RNA-Seq 分析揭示了用 BAd-H5HA 免疫的动物中涉及先天性和适应性免疫的基因的差异表达 (DE)。通过RT-PCR验证了前10个增强基因。一致地,与 HAdV 载体组相比,接种 BAdV 载体的组肺中细胞因子(IL-1α、IL-1β、IL-5、TNF-α、LIF、IL-17、G-CSF、MIP-1β、MCP-1、MIP-2 和 GM-CSF)和 Toll 样受体的水平出现短暂增加。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性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秀基因递送系统。
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.
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期刊: VIRUS RESEARCH
影响因子: 5
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