T4 bacteriophage nanoparticles engineered through CRISPR provide a versatile platform for rapid development of flu mucosal vaccines
文献类型: 外文期刊
第一作者: Li, Mengling
作者: Li, Mengling;Chen, Cen;Wang, Xialin;Guo, Pengju;Feng, Helong;Zhang, Xueqi;Zhang, Wanpo;Gu, Changqin;Peng, Guiqing;Tao, Pan;Li, Mengling;Chen, Cen;Wang, Xialin;Guo, Pengju;Zhang, Xueqi;Peng, Guiqing;Tao, Pan;Feng, Helong;Wen, Guoyuan;Zhu, Jingen;Rao, Venigalla B.;Feng, Yaoyu;Xiao, Lihua
作者机构:
关键词: Mucosal vaccine; Influenza virus; Bacteriophage T4; Mucosal immune responses; CRISPR engineering
期刊名称:ANTIVIRAL RESEARCH ( 影响因子:7.6; 五年影响因子:5.8 )
ISSN: 0166-3542
年卷期: 2023 年 217 卷
页码:
收录情况: SCI
摘要: Vaccines that trigger mucosal immune responses at the entry portals of pathogens are highly desired. Here, we showed that antigen-decorated nanoparticle generated through CRISPR engineering of T4 bacteriophage can serve as a universal platform for the rapid development of mucosal vaccines. Insertion of Flu viral M2e into phage T4 genome through fusion to Soc (Small Outer Capsid protein) generated a recombinant phage, and the Soc-M2e proteins self-assembled onto phage capsids to form 3M2e-T4 nanoparticles during propagation of T4 in E. coli. Intranasal administration of 3M2e-T4 nanoparticles maintains antigen persistence in the lungs, resulting in increased uptake and presentation by antigen-presenting cells. M2e-specific secretory IgA, effector (TEM), central (TCM), and tissue-resident memory CD4+ T cells (TRM) were efficiently induced in the local mucosal sites, which mediated protections against divergent influenza viruses. Our studies demonstrated the mechanisms of immune protection following 3M2e-T4 nanoparticles vaccination and provide a versatile T4 platform that can be customized to rapidly develop mucosal vaccines against future emerging epidemics.
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