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ACS Nano . Mature Dendritic Cell-Derived Extracellular Vesicles are Potent Mucosal Adjuvants for Influenza Hemagglutinin Vaccines

tetano

Editor, Senior Moderator
ACS Nano


. 2025 Jul 1.
doi: 10.1021/acsnano.5c08831. Online ahead of print. Mature Dendritic Cell-Derived Extracellular Vesicles are Potent Mucosal Adjuvants for Influenza Hemagglutinin Vaccines

Chunhong Dong[SUP] 1 [/SUP], Lai Wei[SUP] 1 [/SUP], Wandi Zhu[SUP] 1 [/SUP], Joo Kyung Kim[SUP] 1 [/SUP], Ye Wang[SUP] 1 [/SUP], Priscilla Omotara[SUP] 1 [/SUP], Arini Arsana[SUP] 1 [/SUP], Bao-Zhong Wang[SUP] 1 [/SUP]



Affiliations
Abstract

Immune cell-derived extracellular vesicles (EVs) possess intrinsic immunomodulatory properties, making them potential vaccine adjuvants. Here, we show that EVs from mature bone marrow-derived dendritic cells (mDC-EVs), rather than those from immature dendritic cells (imDC-EVs), are potent mucosal adjuvants for influenza hemagglutinin (HA) vaccines. In vitro, mDC-EVs exhibited intriguing immune-stimulating effects on various antigen-presenting cells, including DCs, macrophages, and B cells. Furthermore, intranasal immunization with mDC-EVs-adjuvanted A/Aichi/2/1968 (H3N2) HA (H3+mDC-EVs) significantly enhanced and expanded both systemic and mucosal antibody and cellular immune responses in female Balb/c mice. These responses offered complete protection against bodyweight loss following homologous and heterologous virus challenges. Mechanistically, H3+mDC-EVs immunization promoted enhanced airway immune cell recruitment, distinct antigen cellular uptake, and rapid activation of B and T cells within 24 h. It also induced robust germinal center reactions and antigen-experienced memory T-cell responses in lung-draining mediastinal lymph nodes 14 days postimmunization. Given their biocompatibility and solid adjuvanticity, mDC-EVs represent a promising adjuvant candidate for mucosal vaccine development.

Keywords: dendritic cell-derived extracellular vesicles; immunoenhancing effect; influenza cross-protection; intranasal vaccination; recombinant protein vaccines.

 
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