T4 bacteriophage nanoparticles engineered through CRISPR provide a versatile platform for rapid development of flu mucosal vaccines

Antiviral Res. 2023 Jul 27:105688. doi: 10.1016/j.antiviral.2023.105688. Online ahead of print.ABSTRACTVaccines 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.PMID:37516153 | DOI:10.1016/j.antiviral.2023.105688

Source: Antiviral Research - July 29, 2023 Category: Virology Authors: Mengling Li Cen Chen Xialin Wang Pengju Guo Helong Feng Xueqi Zhang Wanpo Zhang Changqin Gu Jingen Zhu Guoyuan Wen Yaoyu Feng Lihua Xiao Guiqing Peng Venigalla B Rao Pan Tao Source Type: research