Evaluation of the Lon-deficient Salmonella strain as an oral vaccine candidate.
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 x 10(8) 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.
Kodama
Chie
C
Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, Tokyo 108-8641, Japan.
Eguchi
Masahiro
M
Sekiya
Yukie
Y
Yamamoto
Tomoko
T
Kikuchi
Yuji
Y
Matsui
Hidenori
H
D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D000918:Antibody Specificity; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D001646:Bile / Q000276:immunology; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007371:Interferon-gamma / Q000032:analysis; D007413:Intestinal Mucosa / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D049070:Protease La / Q000172:deficiency / Q000235:genetics; D012480:Salmonella Infections / Q000276:immunology* / Q000517:prevention & control*; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014611:Vaccination
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007071:Immunoglobulin A, Secretory; D007371:Interferon-gamma; D049070:Protease La