口腔微针递送的铁蛋白纳米疫苗可诱导对铜绿假单胞菌的强呼吸道免疫

IF 11.5 1区 医学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Chunting He , Penghui He , Lin Ye, Qiaoran Yang, Yuxuan Ye, Yuwei Wang, Zhaofei Guo, Yangsen Ou, Hairui Wang, Yuanhao Zhao, Shuting Bai, Hongjiao Wei, Guangsheng Du, Xun Sun
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引用次数: 0

摘要

粘膜疫苗通过诱导粘膜表面分泌IgA (sIgA),为抵抗入侵的病原体提供了至关重要的一线防御。虽然基于亚单位抗原的粘膜疫苗提供了更好的安全性,但其发展面临两个巨大的挑战:固有的较差的粘膜免疫原性和低效率的抗原通过粘膜屏障传递。在这里,我们证明了铁蛋白纳米疫苗结合溶解微针通过口腔黏膜免疫对铜绿假单胞菌(PA)感染有效。利用SpyTag/SpyCatcher系统将PA抗原PcrVNH与铁蛋白纳米颗粒结合,构建纳米疫苗。这种微针疫苗显示了有效的粘膜渗透和抗原呈递细胞在渗透部位的招募。值得注意的是,使用的铁蛋白纳米颗粒显示出有效的粘膜佐剂性,这表明抗原摄取的改善,抗原呈递细胞的激活以及粘膜和全身体液和细胞免疫反应的扩增。最后,它诱导呼吸道粘膜分泌物产生有效的sIgA和全身免疫反应,为PA肺部感染提供有效保护。我们的研究结果表明,铁蛋白纳米疫苗联合微针递送是开发安全有效的粘膜亚单位疫苗的一种有前景的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Buccal microneedle-delivered ferritin nanovaccines induce strong respiratory immunity against Pseudomonas aeruginosa

Buccal microneedle-delivered ferritin nanovaccines induce strong respiratory immunity against Pseudomonas aeruginosa

Buccal microneedle-delivered ferritin nanovaccines induce strong respiratory immunity against Pseudomonas aeruginosa
Mucosal vaccines provide a crucial first-line defense against invading pathogens by inducing secretory IgA (sIgA) at mucosal surfaces. While subunit antigen based mucosal vaccines offer improved safety profiles, their development faces two tremendous challenges: inherently poor mucosal immunogenicity and inefficient antigen delivery across mucosal barriers. Here, we demonstrate ferritin nanovaccine incorporated dissolving microneedles are effective against Pseudomonas aeruginosa (PA) infection via buccal mucosal immunization. The nanovaccine was engineered through conjugating the PA antigen PcrVNH to ferritin nanoparticles using SpyTag/SpyCatcher system. This microneedles vaccine demonstrated efficient mucosal penetration and recruitment of antigen-presenting cells at the penetration sites. Notably, the used ferritin nanoparticles showed potent mucosal adjuvanticity as indicated by the improved antigen uptake, activation of the antigen-presenting cells and the amplification of the both mucosal and systemic humoral and cellular immune responses. Finally, it induced potent sIgA production in respiratory mucosal secretions and systemic immune responses, providing effective protection against PA pulmonary infection. Our findings establish ferritin nanovaccines combined with microneedles delivery as a promising strategy for developing safe and effective mucosal subunit vaccines.
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来源期刊
Journal of Controlled Release
Journal of Controlled Release 医学-化学综合
CiteScore
18.50
自引率
5.60%
发文量
700
审稿时长
39 days
期刊介绍: The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System. Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries. Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.
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