Title : Engineered extracellular vesicles vaccines with conserved peptides induce robust immune defense against influenza virus
Abstract:
Influenza viruses are known to cause respiratory illnesses that often lead to mortality and morbidity in humans worldwide. Currently available vaccines, predominantly target highly variable surface glycoproteins, thereby reducing the protective efficacy of vaccine overtime due to continuous antigenic drift and occasional shift. Subsequently, seasonal vaccine needs to be reformulated frequently to provide protective efficacy against emerging strains. Therefore, there is a need to design a vaccine candidate that focuses on conserved viral antigens such as nucleoprotein (NP) that will provide long term immunity, obviating the need for frequent updates of vaccine. Extracellular vesicles have emerged as promising nanocarriers for antigen delivery due to their biocompatibility and robust uptake by antigen presenting cells. Our study focuses on the role of engineered EVs in effectively eliciting cellular immune responses in influenza virus infection. Further, characterization of EVs was performed by western blotting for exosomal markers (CD9 and CD63), Dynamic light scattering (DLS), and transmission electron microscopy (TEM). A highly conserved peptide of NP of influenza virus was selected as an antigenic target and analyzed in vitro. The vaccine candidate was loaded into EVs isolated from HEK293T cells and were delivered to experimental cells, which generated significant immune response as there was increased levels of IFN-γ, IL-2 and IL-17 cytokines. The immunogenic potential of engineered EVs was further evaluated in vivo to confirm the proof of concept. This study provided robust immune response and may serve as effective strategy for next generation vaccines against influenza virus and other pathogens.
