An outer membrane vesicle-adjuvanted oral vaccine protects against lethal, oral Salmonella infection

Abstract

Non-typhoidal salmonellosis, caused by Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common disease worldwide that can be contracted from contact with contaminated food, water, or animal carriers. Salmonellosis is characterized by mild gastrointestinal distress resulting in diarrhea, chills, fever, abdominal cramps, head and body aches, nausea, and vomiting; however, increasing incidences of antibiotic resistant invasive non-typhoidal Salmonella infections makes this a global threat requiring novel treatment strategies such next-generation vaccines. The goal of the current study was to formulate a novel vaccine platform against Salmonella infection that could be delivered orally. To accomplish this, we created a vaccine consisting of Burkolderia pseudomallei outer membrane vesicles (OMVs) which have been shown to act as potent immune mediators and are currently being explored as adjuvants for the next generation of vaccines. We show here that adding OMVs to a heat-killed oral Salmonella vaccine protects against a lethal oral challenge with S. Typhimurium. We show that anti-Salmonella antibodies are induced in response to immunization and demonstrate that bacterial burdens are lessened when OMVs are included in the vaccine. We are currently exploring whether CD4 helper T cells are induced and can contribute to the observed protection as these cells are known to be essential mediators of protective anti-Salmonella immunity. This study represents a new, oral vaccine approach to combatting the increasing problem of invasive Salmonella infections.