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Influenza hemagglutinin subunit vaccines are more effective and offer better cross protection against various influenza virus challenges when combined with a mucosal adjuvant that enhances the body's immune response, according to a study by researchers in the Institute for Biomedical Sciences at Georgia State University.

The study in the journal ACS Nano shows that immune cell-derived extracellular vesicles, specifically those from mature bone marrow-derived dendritic cells (which are crucial for immune responses), rather than those from immature dendritic cells, are potent mucosal adjuvants for influenza hemagglutinin vaccines.

The influenza hemagglutinin subunit vaccine is a type of influenza vaccine that primarily contains the surface protein hemagglutinin of the influenza virus. Mucosal adjuvants are substances that can enhance the body's immune response to foreign materials in the mucosa, such as the surface of the respiratory tract, the study authors explain.

Existing seasonal influenza vaccines have limited effectiveness against evolved virus strains, so next-generation, cross-protective influenza vaccines are urgently needed.

Recombinant protein subunit vaccines have gained attention in vaccine development due to their safety, ease of large-scale manufacturing and affordability. Protein subunit vaccines can be designed to target specific pathogen components, leading to more focused immune responses.

Studies have found that mucosal immunization is a promising strategy against respiratory infectious diseases because it helps prevent the infection and transmission of respiratory pathogens and exhibits potential cross protection. However, the effectiveness of protein vaccines administered mucosally is limited, so there's a need for safe and effective mucosal adjuvants.

This study investigated the potential of extracellular vesicles derived from mature dendritic cells as mucosal adjuvants for influenza hemagglutinin vaccines.

Prior to this study, the mucosal adjuvant potential of extracellular vesicles derived from mature dendritic cells and the underlying mechanisms of action were unknown.

"Immune cell-derived extracellular vesicles, which play crucial roles in intercellular communication and modulating biological responses, are potent mucosal adjuvants for influenza hemagglutinin vaccines," said Bao-Zhong Wang, senior author of the study and Distinguished University Professor in the Institute for Biomedical Sciences at Georgia State.

"These vesicles exhibit intriguing immunostimulatory activity both in vitro and in vivo," Wang said. "Specifically, they effectively activated antigen-presenting cells, macrophages and B cells in vitro, and promoted enhanced recruitment of airway immune cells, early lymphocyte activation and robust germinal center formation in mice."

The study found that intranasal immunization of mice with the influenza hemagglutinin vaccine plus the extracellular vesicle adjuvant from mature bone marrow-derived dendritic cells elicited significant, cross-reactive, and multifaceted humoral and cellular immune responses at both systemic and mucosal sites, conferring complete protection against homologous and heterologous influenza virus challenges.

The researchers point out that extracellular vesicles derived from mature dendritic cells have gained significant attention in immunotherapy and vaccine development because they have a variety of immunologically active molecules crucial for effective presentation of antigens (foreign substances that induce an immune response in the body), as well as cell adhesion and fusion.

"These findings underscore the potential of extracellular vesicles from mature bone marrow-derived dendritic cells as a promising adjuvant or immunomodulatory target for the development of mucosal vaccines," said Chunhong Dong, first author of the study and a postdoctoral fellow in the Institute for Biomedical Sciences at Georgia State.

"Given their biocompatibility and solid adjuvanticity, mature bone marrow-derived dendritic cells represent a promising adjuvant candidate for mucosal vaccine development."

Additional authors of the study include Lai Wei, Wandi Zhu, Joo Kyung Kim, Ye Wang, Priscilla Omotara and Arini Arsana of the Institute for Biomedical Sciences at Georgia State.