The use of outer membrane vesicles as novel, mucosal adjuvants
Many pathogens first enter the body via mucosal surfaces where they can then invade and disseminate systemically to cause disease. Despite this, most vaccines are given parenterally and are unable to induce mucosal immunity. Immunizing directly at the mucosa could solve this problem, however delivering vaccines at these surfaces often doesn’t invoke robust immunity. One way to alleviate this is to use adjuvants that can evoke an immune response. Most adjuvants, like aluminum salts, are unable to induce mucosal immunity and so novel adjuvants must be employed. Outer membrane vesicles (OMVs) from Burkholderia pseudomallei are potent immune mediators and have been shown to have adjuvant capabilities. The goal of this study is to highlight the role of OMVs as a novel adjuvant that can be used in the next generation of mucosal vaccines. To test this, we created an OMV-adjuvanted vaccine against Salmonella Typhimurium and used the model antigens, 2W1S and ovalbumin (OVA) to test mucosal vaccinations. An oral vaccine against S. Typhimurium adjuvanted with OMVs showed protection against lethal challenge in addition to evoking antigen specific CD4 T cells, B cells, and anti-Salmonella antibodies. These antibodies induced greater bacterial killing in macrophages. An intranasal vaccine using 2W1S and OVA elicited both antigen specific CD4 and CD8 T cells, B cells, and anti-OVA antibodies. These studies highlight how OMVs can be used in two different mucosal routes and elicit similar responses despite being delivered with different types of vaccines – inactivated whole-cell vs. protein subunit. This study represents the first time that B. pseudomallei OMVs have been used in a mucosal vaccine and highlights the potential to create new mucosal adjuvants that can be used in the next generation of vaccines.