Development of a cost-effective vaccine candidate with outer membrane vesicles of a tolA-disrupted Shigella boydii strain

Vaccine
Soma MitraHemanta Koley

Abstract

Our previous studies on outer membrane vesicles based vaccine development against shigellosis, revealed the inability of Shigella to release significant amount of vesicles naturally, during growth. Disruption of tolA, one of the genes of the Tol-Pal system of Gram negative bacterial membrane, has increased the vesicle release rate of a Shigella boydii type 4 strain to approximately 60% higher. We also noticed the vesicles, released from tolA-disrupted strain captured more OmpA protein and lipopolysaccharide, compared to the vesicles released from its wild type prototype. Six to seven weeks old BALB/c mice, immunized with 25 μg of three oral doses of the vesicles, released by tolA mutant, conferred 100% protection against lethal homologous challenge through nasal route, compared to only 60% protection after the same dose of wild type immunogen. Mice, immunized with the vesicles from tolA-mutant, manifested significant secretion of mucosal IgG and IgA. A sharp and significant response of pro-inflammatory cytokines (TNF-α, IL-6, IFN-γ) were also observed in the lung lavage of these groups of mice, within 6h post challenge; but at 24h, these inflammatory cytokines showed the sign of subsidence and the system was taken over by the r...Continue Reading

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Citations

Oct 26, 2016·Cellular Microbiology·Rishi D Pathirana, Maria Kaparakis-Liaskos
Jul 20, 2017·Journal of Medical Microbiology·Yadira PastorCarlos Gamazo
Jan 1, 2016·Molecular Membrane Biology·Deepak Anand, Arunima Chaudhuri
Oct 13, 2020·Critical Reviews in Microbiology·Roghayeh MohammadzadehSaman Soleimanpour
Aug 18, 2020·Applied and Environmental Microbiology·Kotaro TakakiYosuke Tashiro
Sep 29, 2019·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Linglei JiangRaymond M Schiffelers
Mar 17, 2021·Molecular Immunology·William J GilmoreMaria Kaparakis-Liaskos
Mar 30, 2021·Advanced Drug Delivery Reviews·Mina MehannyGregor Fuhrmann

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