Rewiring of one carbon metabolism in Salmonella serves as an excellent live vaccine against systemic salmonellosis. Issue 50 (29th November 2018)

• Record Type: Journal Article
• Authors: Datey, Akshay; Shreenivas, Meghanashree; Chandrasekharan, Giridhar; Joseph, Jeswin; Sah, Shivjee; Aluri, Srinivas; Saha, Sankhanil; Varshney, Umesh; Chakravortty, Dipshikha
• Is Part Of: Vaccine. Volume 36:Issue 50(2018)
• Page Start: 7715
• Page End: 7727
• Publication Date: 2018-11-29
• Subjects: Salmonella Typhimurium -- One-carbon metabolism -- Live attenuated vaccine -- Murine model -- Systemic salmonellosis; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2018.10.079
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Development of re-engineered one-carbon metabolism mutant in STM as vaccine. Vaccine strain exhibits attenuation. Highly immunogenic vaccine and functions at lower doses. Pregnant, geriatric and neonates could be protected with this vaccine. Abstract: Live attenuated vaccines are superior to the killed or subunit vaccines. We designed a Salmonella Typhimurium strain by deleting folD gene (encoding methylenetetrahydrofolate dehydrogenase-cyclohydrolase) in the presence of a heterologous fhs gene (encoding formyltetrahydrofolate synthetase) and tested its vaccine potential under stringent conditions of lethal and sub-lethal challenges with virulent Salmonella in the murine model. The efficacy of the vaccine in conferring protection against Salmonella infection was determined in a wide range of host conditions of systemic infection, corresponding to human young adults, neonates, geriatric age and, importantly, to the immune compromised state of pregnancy. The standardized vaccination regime comprised a primary dose of 10 4 CFU/animal followed by a booster dose of 10 2 CFU/animal on day 7. Challenge with the virulent pathogen was done at day 7 post-administration of the booster. Subsequently, the mortality, morbidity, systemic colonization, antibody response and cytokine profiling were determined. The vaccinated cohort showed a strong protection against virulent pathogen in all models tested. The serum anti- Salmonella antibody titers and cytokine levels were significantly higher in the vaccinated cohort compared to the mock vaccinated cohort. Thus, we report the development and validation of a live attenuated vaccine candidate conferring excellent protection against Salmonellosis and typhoid fever.