Rewiring of one carbon metabolism in Salmonella serves as an excellent live vaccine against systemic salmonellosis

Akshay Datey, Meghanashree Shreenivas, Giridhar Chandrasekharan, Jeswin Joseph, Shivjee Sah, Srinivas Aluri, Sankhanil Saha, Umesh Varshney, Dipshikha Chakravortty

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7715-7727
Number of pages13
JournalVaccine
Volume36
Issue number50
DOIs
StatePublished - Nov 29 2018
Externally publishedYes

Keywords

  • Live attenuated vaccine
  • Murine model
  • One-carbon metabolism
  • Salmonella Typhimurium
  • Systemic salmonellosis

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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