Evaluation of the Lon-Deficient Salmonella Strain as an Oral Vaccine Candidate

• Published in: Microbiology and immunology 2005-01, Vol.49 (12), p.1035-1045
• Main Authors: Kodama, Chie, Eguchi, Masahiro, Sekiya, Yukie, Yamamoto, Tomoko, Kikuchi, Yuji, Matsui, Hidenori
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Antibodies, Bacterial - analysis; Antibody Specificity; Bacterial Vaccines - administration & dosage; BALB/c; Bile - immunology; C57BL/6; Immunoglobulin A, Secretory - analysis; Interferon-gamma - analysis; Intestinal Mucosa - immunology; Macrophages, Peritoneal - microbiology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; oral vaccine; Protease La - deficiency; Protease La - genetics; salmonella; Salmonella enterica; Salmonella Infections - immunology; Salmonella Infections - prevention & control; Salmonella typhimurium - genetics; Salmonella typhimurium - immunology; Spleen - immunology; Vaccination
• ISSN: 0385-5600; 1348-0421
• DOI: 10.1111/j.1348-0421.2005.tb03700.x

We evaluated the efficacy of CS2022 (the Lon protease‐deficient mutant strain of Salmonella enterica serovar Typhimurium) as a candidate live oral vaccine strain against subsequent oral challenge with a virulent strain administered to BALB/c and C57BL/6 mice. CS2022 persistently resided in the spleen, mesenteric lymph nodes, Peyer's patches, and cecum of both strains of mice after a single oral inoculation with 1 × 108 colony‐forming units. Finally, CS2022 almost disappeared from each tissue sample by week 12 in BALB/c mice, whereas CS2022 still resided in each tissue type at week 12 after inoculation of C57BL/6 mice. A significant increase in the serovar Typhimurium lipopolysaccharide‐specific secretory immunoglobulin A (s‐IgA), as measured for one of the mucosal immune responses, was detected in bile and intestinal samples of both strains of immunized mice at week 4 after immunization. In addition, the expression of gamma interferon mRNA in the spleens of both strains of immunized mice, especially those of C57BL/6 mice, was significantly increased at week 4 after immunization and was boosted during the following 5 days after the challenge was administered to the mice. Furthermore, peritoneal macrophages isolated from immunized mice at week 4 after immunization exhibited an increase in intracellular killing activity against both virulent and avirulent Salmonella. The present results suggested that salmonellae‐specific s‐IgA on the mucosal surfaces induced by immunization with CS2022 generally prevented mice from succumbing to an oral challenge with a virulent strain. Simultaneously, CS2022 promoted the protective immunity associated with macrophages in both strains of mice.