LT(R192G), a non-toxic mutant of the heat-labile enterotoxin of Escherichia coli, elicits enhanced humoral and cellular immune responses associated with protection against lethal oral challenge with Salmonella spp.
In the current study we examined the ability of a novel mucosal adjuvant, LT(R192G), to enhance the humoral and cellular immune responses against killed Salmonella spp. and to affect protection against lethal oral challenge with wild-type organisms. Mice orally immunized with killed S. dublin in conjunction with LT(R192G) were protected against lethal oral challenge and had higher IFN-gamma, IL-2 and IgG responses than did mice orally immunized with killed S. dublin alone which were not protected. This study demonstrates that the function of LT(R192G) in protection against typhoid-like disease is to upregulate/enhance the Th1 arm of the immune response against killed organisms. When used as a mucosal adjuvant, LT(R192G) enables the use of killed bacteria or viruses as vaccines by enhancing the overall humoral and cellular host immune response to these organisms, especially the Th1 arm of the immune response. These findings have significant implications for vaccine development and further support the potential of LT(R192G) to function as a safe, effective adjuvant for mucosally administered vaccines.
Chong
C
C
Department of Microbiology and Immunology, Tulane University Medical Center, New Orleans, LA 70112, USA.
Friberg
M
M
Clements
J D
JD
D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D000918:Antibody Specificity; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D029968:Escherichia coli Proteins; D005243:Feces; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009500:Neutralization Tests; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000517:prevention & control*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D008070:Lipopolysaccharides; D007371:Interferon-gamma; C027538:heat-labile enterotoxin, E coli