Killed but Metabolically Active Salmonella typhimurium: Application of a New Technology to an Old Vector

• Published in: The Journal of infectious diseases Vol. 195; no. 8; pp. 1203 - 1211
• Main Authors: Lankowski, Alexander J., Hohmann, Elizabeth L.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.04.2007; University of Chicago Press
• Subjects: Animals; Antigens; Antigens, Bacterial - metabolism; Bacteria; Bacterial Proteins - analysis; Bacterial Proteins - biosynthesis; Bacteriology; Biological and medical sciences; Diseases; Dose-Response Relationship, Radiation; Female; Fundamental and applied biological sciences. Psychology; Infectious diseases; Macrophages - microbiology; Medical sciences; Metabolism; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Mutation; Psoralens; Radiation dosage; Salmonella; Salmonella Infections - immunology; Salmonella typhimurium; Salmonella typhimurium - genetics; Salmonella typhimurium - immunology; Salmonella typhimurium - metabolism; Salmonella typhimurium - pathogenicity; Salmonella Vaccines; Spleen - physiology; Sulfur Isotopes - analysis; Transcriptional regulatory elements; Ultraviolet Rays; Vaccination; Vaccines, Inactivated; Virulence; Infection; Bacteria; Microbiology; Salmonella typhimurium; Vector; Enterobacteriaceae
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/512618

Previous studies have shown that attenuated salmonellae utilized as vaccine vectors engender strong immune responses; however, balancing immunogenicity with reactogenicity remains problematic. Recent work in other bacteria has shown that photochemical treatment of DNA excision repair mutants (ΔuvrAB) renders organisms "killed but metabolically active" (KBMA). Here, we extend this concept to Salmonella typhimurium. A strain of attenuated S. typhimurium previously evaluated in human volunteers was further deleted for uvrAB genes and designated CKS362. Photochemical treatment of CKS362 resulted in significant inactivation. These KBMA organisms were metabolically active as shown by radioactive methionine incorporation and lactate dehydrogenase activity. In mice inoculated intraperitoneally, KBMA CKS362 was markedly less reactogenic and stimulated a humoral immune equivalent to its live counterpart. Because the parental strain has previously been found to elicit strong immune responses to Salmonella antigens, we propose CKS362 as a prototype strain to test the immunogenicity of KBMA organisms in humans.