Mature Dendritic Cell-Derived Extracellular Vesicles are Potent Mucosal Adjuvants for Influenza Hemagglutinin Vaccines
Chunhong Dong, Lai Wei, Wandi Zhu, Joo Kyung Kim, Ye Wang, Priscilla Omotara, Arini Arsana, Bao‐Zhong Wang
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.