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

• Published in: Antiviral research Vol. 217; p. 105688
• Main Authors: Li, Mengling, Chen, Cen, Wang, Xialin, Guo, Pengju, Feng, Helong, Zhang, Xueqi, Zhang, Wanpo, Gu, Changqin, Zhu, Jingen, Wen, Guoyuan, Feng, Yaoyu, Xiao, Lihua, Peng, Guiqing, Rao, Venigalla B., Tao, Pan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-09-2023
• Subjects: Bacteriophage T4; CRISPR engineering; Influenza virus; Mucosal immune responses; Mucosal vaccine; M2e; Mucosal vaccine; Influenza virus; Soc; BALF; CRISPR engineering; Bacteriophage T4; Mucosal immune responses; TEM; TRM; MLN; DC
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2023.105688

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.
[Display omitted]
•A CRISPR/Cas-engineered universal T4 phage platform for mucosal vaccine development.•Antigen-decorated T4 phage nanoparticles mediate antigen persistence in the lung.•Influenza viral M2e-T4 nanoparticles promote antigen presentation in the lung.•Intranasal delivery of M2e-T4 nanoparticles elicits robust mucosal immune responses.•A M2e-T4 mucosal vaccine confers mice full protection against divergent flu viruses.