A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa

• Published in: mSphere Vol. 4; no. 2
• Main Authors: Aguilera-Herce, Julia, García-Quintanilla, Meritxell, Romero-Flores, Rocío, McConnell, Michael J, Ramos-Morales, Francisco
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 17.04.2019
• Subjects: Antibiotic resistance; Antibiotics; Antibodies; Antigens; Clinical trials; Cystic fibrosis; Cytokines; Experiments; Inflammation; Laboratories; Nosocomial infections; Opportunist infection; Pathogens; Plasmids; Proteins; Pseudomonas aeruginosa; Salmonella; Salmonella enterica; Serum levels; Therapeutics and Prevention; Tumor necrosis factor-TNF; Vaccines; Spain; Pseudomonas aeruginosa; PcrV; SseJ; Salmonella-delivered vaccines; type III secretion
• ISSN: 2379-5042; 2379-5042
• DOI: 10.1128/mSphere.00116-19

is a common Gram-negative opportunistic pathogen that is intrinsically resistant to a wide range of antibiotics. The development of a broadly protective vaccine against remains a major challenge. Here, we used an attenuated strain of serovar Typhimurium as a vehicle to express antigens. A fusion between the type III secretion effector protein SseJ and the antigen PcrV expressed under the control of the promoter was translocated by into host cells and elicited the generation of specific antibodies in mice. Mice immunized with attenuated expressing this fusion had reduced bacterial loads in the spleens and lungs and lower serum levels of proinflammatory cytokines than control mice after infection. Importantly, immunized mice also showed significantly enhanced survival in this model. These results suggest that type III secretion effectors of are appropriate carriers in the design of a live vaccine to prevent infections caused by The Gram-negative bacterium is an important opportunistic pathogen that causes infections in cystic fibrosis and hospitalized patients. Therapeutic treatments are limited due to the emergence and spread of new antibiotic-resistant strains. In this context, the development of a vaccine is a priority. Here, we used an attenuated strain of serovar Typhimurium as a vehicle to express and deliver the antigen PcrV. This vaccine induced the generation of specific antibodies in mice and protected them from lethal infections with This is an important step toward the development of an effective vaccine for the prevention of infections caused by in humans.