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

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

  • Biomaterials. 2026 Aug:331:124113. doi: 10.1016/j.biomaterials.2026.124113.
Yinhe Xia 1,  Zhou Xu 2,  Ruilong Song 3,  Weijie Wang 2,  Yuli Li 2,  Ling Xu 2,  Changchao Huan 4,  Peng Cao 5,  Gang Chen 6
Affiliations

Affiliations

  • 1 Shandong Provincial Key Medical and Health Laboratory of Neuro-oncology of Innovative Integrated Medicine, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266042, China; School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, 266113, China; Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China; State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Taicang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Taicang, 215499, China.
  • 2 School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, 266113, China.
  • 3 Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China.
  • 4 Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China. Electronic address: [email protected].
  • 5 State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China. Electronic address: [email protected].
  • 6 Shandong Provincial Key Medical and Health Laboratory of Neuro-oncology of Innovative Integrated Medicine, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266042, China; School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, 266113, China. Electronic address: [email protected].
PMID: 41795404 DOI: 10.1016/j.biomaterials.2026.124113
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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