结核分枝杆菌EsxV脂质体纳米颗粒亚单位疫苗的制备及免疫学特性
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陕西省重点研发计划(2022ZDLSF01-07);国家自然科学基金(81971560,82272343);国家“十三五”重大专项(2018ZX10302302002004)


Preparation of Mycobacterium tuberculosis EsxV lipid nanoparticles subunit vaccine and its immunological characteristics
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    摘要:

    本研究旨在制备脂质体纳米颗粒(lipid nanoparticles,LNP)为载体的结核分枝杆菌(Mycobacterium tuberculosis,Mtb)抗原EsxV亚单位疫苗,明确该疫苗经黏膜免疫诱导的免疫应答水平。采用薄膜分散法制备包裹蛋白EsxV和c-di-AMP的LNP (EsxV:C:L),并对其包封率、LNP形态、粒径、表位电荷及多相分散指数进行了检测。EsxV:C:L滴鼻免疫BALB/c小鼠,检测免疫后血清和黏膜抗体、肺或脾细胞因子转录及分泌水平、肺T细胞亚群细胞比例。结果成功获得大小均一、呈球状、带负电的EsxV:C:L LNP亚单位疫苗。与EsxV:C相比,EsxV:C:L鼻黏膜接种可诱导小鼠呼吸道黏膜sIgA水平增加,脾细胞因子IL-2分泌水平升高,提高中央记忆T细和组织驻留T细胞的比例。综上,EsxV:C:L经黏膜免疫,可诱导更强的黏膜免疫和记忆性T细胞免疫应答,可能提供更好的抗Mtb感染的保护作用。

    Abstract:

    To prepare a lipid nanoparticle (LNP)-based subunit vaccine of Mycobacterium tuberculosis (Mtb) antigen EsxV and study its immunological characteristics, the LNP containing EsxV and c-di-AMP (EsxV:C:L) was prepared by thin film dispersion method, and its encapsulation rate, LNP morphology, particle size, surface charge and polyphase dispersion index were measured. BALB/c mice were immunized with EsxV:C:L by nasal drops. The levels of serum and mucosal antibodies, transcription and secretion of cytokines in lung and spleen, and the proportion of T cell subsets were detected after immunization. EsxV:C:L LNPs were obtained with uniform size and they were spherical and negatively charged. Compared with EsxV:C immunization, EsxV:C:L mucosal inoculation induced increased sIgA level in respiratory tract mucosa. Levels of IL-2 secreted from spleen and ratios of memory T cells and tissue-resident T cells in mice were also elevated. In conclusion, EsxV:C:L could induce stronger mucosal immunity and memory T cell immune responses, which may provide better protection against Mtb infection.

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白鹭,路延之,宁唤唤,康亚莉,谢燕玲,康健,李雪,崔若囡,韦垠,刘月芹,柏银兰. 结核分枝杆菌EsxV脂质体纳米颗粒亚单位疫苗的制备及免疫学特性[J]. 生物工程学报, 2023, 39(10): 4085-4097

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  • 收稿日期:2023-04-03
  • 录用日期:2023-06-28
  • 在线发布日期: 2023-10-17
  • 出版日期: 2023-10-25
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