Exp Mol Med.  2000 Jun;32(2):72-78.

The mucosal adjuvanticity of two nontoxic mutants of Escherichia coli heat-labile enterotoxin varies with immunization routes

• Park EJ
• Chang JH
• Kim JS
• Yum JS
• Chung SI

Abstract

Escherichia coli heat-labile enterotoxin (LT), which causes a characteristic diarrhea in humans and animals, is a strong mucosal immunogen and has powerful mucosal adjuvant activity towards coadministered unrelated antigens. Here we report the different mucosal adjuvanticity of nontoxic LT derivatives, LTS63Y and LTdelta110/112, generated by immunizing through two different mucosal routes. Intragastric (IG) immunization with Helicobacter pylori urease alone resulted in poor systemic IgG and IgA responses and no detectable local secretory IgA, but IG co-immunization with urease and LTdelta110/112 induced high titers of urease-specific local secretory IgA and systemic IgG and IgA, comparable to those induced by wild-type LT. LTS63Y showed far lower adjuvant activity towards urease than LTdelta110/112 in IG immunization, but was more active than LTdelta110/112 in inducing immune responses to urease by intranasal (IN) immunization. LTdelta110/112 predominantly enhanced the induction of urease-specific IgG1 levels following IG immunization, whereas LTS63Y induced high levels of IgG1, IgG2a and IgG2b following IN immunization. In addition, quantitative H. pylori culture of stomach tissue following challenge with H. pylori demonstrated a 90-95% reduction (p < 0.0002) in bacterial burden in mice immunized intranasally with urease using either mutant LT as an adjuvant. These results indicate that the mechanism(s) underlying the adjuvant activities of mutant LTs towards coadmnistered H. pylori urease may differ between the IN and IG mucosal immunization routes.

Keyword

LTS63Y; LTD110/112; secretory IgA; mucosal adjuvant

MeSH Terms

Adjuvants, Immunologic/administration & dosage*
Administration, Intranasal
Animal
Bacterial Toxins/immunology*
Bacterial Toxins/genetics
Bacterial Toxins/administration & dosage
Enterotoxins/immunology*
Enterotoxins/genetics
Enterotoxins/administration & dosage
Enzyme-Linked Immunosorbent Assay
Escherichia coli*
Feces
Female
Gastric Mucosa/microbiology
Gastric Mucosa/immunology*
Helicobacter pylori
Human
IgA, Secretory/immunology*
IgG/immunology
Mice
Mice, Inbred BALB C
Mutagenesis, Site-Directed
NAD+ ADP-Ribosyltransferase/immunology
NAD+ ADP-Ribosyltransferase/genetics
Nasal Mucosa/immunology*
Point Mutation
Urease/immunology*
Urease/administration & dosage
Vaccination*