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
作者： Li, Mengling 1 ; Chen, Cen 1 ; Wang, Xialin 1 ; Guo, Pengju 1 ; Feng, Helong 1 ; Zhang, Xueqi 1 ; Zhang, Wanpo 1 ; Gu, Changqin 1 ; Zhu, Jingen 4 ; Wen, Guoyuan 3 ; Feng, Yaoyu 5 ; Xiao, Lihua 5 ; Peng, Guiqing 1 ; Rao, Venigalla B. 4 ; Tao, Pan 1 ;
作者机构： 1.Huazhong Agr Univ, Coll Vet Med, Cooperat Innovat Ctr Sustainable Pig Prod, State Key Lab Agr Microbiol,Key Lab Prevent & Cont, Wuhan 430070, Hubei, Peoples R China
2.Hubei Hongshan Lab, Wuhan 430070, Hubei, Peoples R China
3.Hubei Acad Agr Sci, Inst Anim Husb & Vet Sci, Wuhan 430070, Hubei, Peoples R China
4.Catholic Univ Amer, Bacteriophage Med Res Ctr, Dept Biol, Washington, DC 20064 USA
5.South China Agr Univ, Coll Vet Med, Key Lab Zoonosis, Minist Agr, Guangzhou 510642, Peoples R China
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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