Development of active bivalent vaccines against enteropathogenic strains.

Rosario

Congreso; Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2023

Foodborne bacterial diseases are among the first five causes of death in children under 5 years old and immunosuppresed patients. In previously studies we demonstrated that, in the NOA region, Shigella is the prevalent pathogen, being Shigella flexneri the most frequently isolated, mainly in the population from 3 to 5 years old. The study of the antibiotic resistance profile (ARP) revealed that the majority of clinical isolates (CI) were presented as Multidrug Resistant (MDR). Therefore, the development of bivalent vaccines with genetically modified microorganisms represents an excellent strategy to combat these diseases, since they can induce an effective immune response not only against pathogens of the same genus and species (attenuated vaccines) but also against phylogenetically related pathogens (recombinant vaccines). The results obtained in our laboratory on the study of Salmonella Typhimurium strains attenuated in virulence, indicated that these mutants can be the basis for the bivalent vaccines development. For this purpose, antigen genes selected from analyzed Shigella’ CI were cloned in specialized vectors, containing elements of the Salmonella’ SPI2 to control its expression and secretion.. The obtained constructions were introduced into the attenuated strain, and the correct expression and secretion of the recombinant antigens was studied. In addition, new attenuated strains derived from the previously studied were obtained, and them the protection conferred against virulent CI of different Salmonella serovars was evaluated. Our results demonstrated that the S. Typhimurium and Enteritidis CI established the infection on BALB/C mice (orally inoculated) during the first week postinfection (p.i.). Meanwhile, mice infected with the attenuated strains survived up to 15 days p.i., even after receiving a second challenge with the both virulent CI. Additionally, the immune response produced in challenged mice was studied. Our results indicated that the attenuated strains induce host immunity against S. Typhimurium and Enteritidis serovars.