Development of surface engineered antigenic exosomes as vaccines for respiratory syncytial virus

Abstract

Abstract Human respiratory syncytial virus (HRSV) is one of the main drivers of lower respiratory tract illness in infants and young children worldwide. There are no licensed vaccines for HRSV available. Exosomes are cell-derived extracellular nanovesicles containing various biomolecules for intracellular communication. Exosomes secreted by antigen presenting cells such as dendritic cells can elicit immune responses by carrying MHC-I with antigenic peptide complex and other co-stimulating factors. Therefore, exosomes have emerged as potential vaccines to prevent viral infections or to treat cancers. Our prior work has demonstrated that a PDMS microfluidic culture chip device can be used to generate dendritic cell-derived tumor antigenic exosomes, with the capacity to activate tumor-specific CD8+ T cells. Herein, we further extended the work to surface engineer dendritic cell-derived exosomes with antigenic peptides from RSV (M187–195 and NS161–75). A mouse model of RSV infection was used to define the immunogenicity of surface engineered exosomes for activating virus-specific immune responses in vitro and in vivo. In vitro assays demonstrated that surface engineered exosomes successfully carried the engineered peptides of interest and had the capacity to elicit IFNγ production by activated, virus-specific CD8+ T cells. However, vaccination with engineered exosomes did not prime an in vivo activation of antigen-specific CD8+ T cell response, although surface engineered exosomes exhibit the safe administration. Additional experiments are necessary to optimize the potency of surface engineered exosomes as a vaccine platform for the prevention of viral infections such as RSV.