Datey, Akshay ; Shreenivas, Meghanashree ; Chandrasekharan, Giridhar ; Joseph, Jeswin ; Sah, Shivjee ; Aluri, Srinivas ; Saha, Sankhanil ; Varshney, Umesh ; Chakravortty, Dipshikha (2018) Rewiring of one carbon metabolism in Salmonella serves as an excellent live vaccine against systemic salmonellosis Vaccine, 36 (50). pp. 7715-7727. ISSN 0264-410X
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Official URL: http://doi.org/10.1016/j.vaccine.2018.10.079
Related URL: http://dx.doi.org/10.1016/j.vaccine.2018.10.079
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 104 CFU/animal followed by a booster dose of 102 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.
Item Type: | Article |
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Source: | Copyright of this article belongs to Elsevier Science. |
Keywords: | Salmonella typhimurium; One-Carbon Metabolism; Live Attenuated Vaccine; Murine Model; Systemic Salmonellosis. |
ID Code: | 118250 |
Deposited On: | 19 May 2021 11:07 |
Last Modified: | 19 May 2021 11:07 |
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