The Potential Salmonella aroA– Vaccine Strain Is Safe and Effective in Young BALB/c MiceBurns-Guydish S.M. · Zhao H. · Stevenson D.K. · Contag C.H.
aDivision of Neonatal and Developmental Medicine, Department of Pediatrics, and bDepartments of Microbiology and Immunology, and Radiology, Stanford University School of Medicine, Stanford, Calif., USA
Background: Due to the increased susceptibility of neonates to pathogens including those with mutations, the use of live vaccine strategies in the human population may present a potential risk to the young. Objectives: The specific aim of this study was to assess the risk that prospective Salmonella enterica serovar Typhimurium vaccine strains pose for the neonate and determine whether the strains are an effective vaccine by assessing the adaptive immune response. Methods: To evaluate the susceptibility of young mice to potential vaccine strains, S. typhimuriumaroA– and ΔphoP mutant strains were labeled by chromosomal insertion of the lux operon – this serves as a readily traceable marker of infection using noninvasive imaging methods. BALB/c mice ages 1, 2, 4, and 6 weeks of age were fed the bioluminescent aroA– or ΔphoP strains and the course of infection was monitored by in vivobioluminescence imaging. In addition, blood samples were collected post-inoculation to assess the IgG response of mice to S. typhimurium LPS. Results: Young BALB/c mice were not susceptible to the aroA– strain in contrast to their susceptibility to the ΔphoP strain at a dose of 109 colony forming units. Delivery by oral feeding of the aroA– and ΔphoP strains in young mice also produced a robust IgG anti-LPS response. Conclusion: Here, we report that young 2-week-old mice orally fed the bioluminescent aroA–S. typhimurium strain were not susceptible to infection and elicited a protective immune response.
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