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Biomaterials . Engineered bacteriophage nanoassemblies in vivo stabilize DC-T cell immune synapse for high-performance influenza vaccination

tetano

Editor, Senior Moderator
Biomaterials


. 2026 Mar 4:331:124113.
doi: 10.1016/j.biomaterials.2026.124113. Online ahead of print.
Engineered bacteriophage nanoassemblies in vivo stabilize DC-T cell immune synapse for high-performance influenza vaccination

Yinhe Xia[SUP] 1 [/SUP], Zhou Xu[SUP] 2 [/SUP], Ruilong Song[SUP] 3 [/SUP], Weijie Wang[SUP] 2 [/SUP], Yuli Li[SUP] 2 [/SUP], Ling Xu[SUP] 2 [/SUP], Changchao Huan[SUP] 4 [/SUP], Peng Cao[SUP] 5 [/SUP], Gang Chen[SUP] 6 [/SUP]


Affiliations
Abstract

T cell activation by dendritic cells (DCs) requires the formation of a stable immune synapse (IS). The objective of this study was to develop a vaccination approach by targetedly regulating DC-T cell synaptic interactions in vivo. We constructed bacteriophage nanoassemblies to deliver antigen-encoding sequences into DC cytoplasm and enhance DC-T cell IS stability in vivo, thereby boosting vaccine potency. Specifically, influenza hemagglutinin stem gene was inserted into the genome and DC-targeting peptide was fused to the sidewall of bacteriophages. Then, bacteriophages acted as surfactants to cover hydrophobic particles, within which sodium/proton pump inhibitors were encapsulated to regulate intercellular adhesion molecule 1 (ICAM-1) membrane positioning for stabilizing IS. The size-controlled nanoassemblies inhibited internalization of ICAM-1 via activating the NF-κB, PI3K-AKT, and RhoA-ROCK signaling pathways. Immunization with the nanoassemblies triggered robust T cell and antibody responses against influenza virus, leading to complete protection and long-term immune memory in infected mice. In sum, our results highlight the feasibility for improving vaccine protective potency via targeted enhancement of the IS stability between DCs and T cells in vivo. Given their flexibility and commonality, the bacteriophage nanoassemblies can be readily tailored for the development of various vaccine formulations against other pathogens.

Keywords: Bacteriophage; Immune synapse; Influenza vaccines; Vaccine delivery.

 
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