An Outer Membrane Vesicle-Adjuvanted Oral Vaccine Protects Against Lethal, Oral Salmonella Infection

Abstract

Non-typhoidal salmonellosis, caused by Salmonella enterica serovar Typhimurium is a common fecal-oral disease characterized by mild gastrointestinal distress resulting in diarrhea, chills, fever, abdominal cramps, head and body aches, nausea, and vomiting. Increasing incidences of antibiotic resistant invasive non-typhoidal Salmonella infections makes this a global threat requiring novel treatment strategies including 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 Salmonella-specific vaccine adjuvanted with Burkholderia pseudomallei outer membrane vesicles (OMVs). We show that adding OMVs to a heat-killed oral Salmonella vaccine (HKST + OMVs) protects against a lethal, oral challenge with Salmonella. Further, we show that opsonizing anti-Salmonella antibodies are induced in response to immunization and that CD4 T cells and B cells can be induced when OMVs are used as the oral adjuvant. This study represents a novel oral vaccine approach to combatting the increasing problem of invasive Salmonella infections.

Current vaccine strategies and novel approaches to combatting Francisella infection

“…OMVs are being explored in a variety of contexts as nanoparticle vaccines, including in the FDA-approved vaccine for meningococcal group B disease, Bexsero [ 90 ]. Other work has shown that the same OMVs can be both a vaccine and an adjuvant, thus potentially behaving as a self-adjuvanting antigen delivery system [ 89 , 91 – 93 ]. OMVs from the closely related F. novicida may be one novel vaccine approach for combatting tularemia.…”

The Role of Bacterial Extracellular Vesicles in the Immune Response to Pathogens, and Therapeutic Opportunities

“…By fusing S. Typhimurium EVs with S. flexneri polysaccharide determinants, protection of mice against a challenge with virulent bacteria was obtained [ 189 ]. Other authors have proposed using EVs from Burkholderia pseudomallei as an adjuvant for a heat-killed S. Typhimurium-based vaccine, and this formulation protected mice against a lethal dose of the bacterium [ 190 ].…”

Potential Applications of Microparticulate-Based Bacterial Outer Membrane Vesicles (OMVs) Vaccine Platform for Sexually Transmitted Diseases (STDs): Gonorrhea, Chlamydia, and Syphilis

“…Their strategy involved mutational inactivation of the MsbB (LpxM) lipid A acyltransferase to generate OMVs of reduced endotoxicity from Escherichia coli (E. coli) O157:H7. The results suggest that by using genetic engineeringbased approaches, the native OMVs could be modified to have both intrinsically low endotoxicity and a foreign epitope tag to establish a platform technology for developing multifunctional vaccine delivery vehicles [48][49][50][51].…”