This Article Full Text (PDF) Other Versions of this Article: IAI.01009-06v1 75/2/621    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nawar, H. F. Articles by Connell, T. D. Search for Related Content PubMed PubMed Citation Articles by Nawar, H. F. Articles by Connell, T. D.

 Previous Article  |  Next Article 

Infect. Immun. doi:10.1128/IAI.01009-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Mutants of Type II Heat-Labile Enterotoxin LT-IIa With Altered Ganglioside-Binding Activities and Diminished Toxicity are Potent Mucosal Adjuvants

The Witebsky Center for Microbial Pathogenesis and Immunology, The Department of Microbiology and Immunology, University at Buffalo, Buffalo, NY

^* To whom correspondence should be addressed. Email: connell{at}acsu.buffalo.edu.

	Abstract

LT-IIa, a type II heat-labile enterotoxin of Escherichia coli, is closely related in structure and function to cholera toxin and LT-I, the type I heat-labile enterotoxins of Vibrio cholerae and enterotoxigenic E. coli, respectively. While LT-IIa is a potent systemic and mucosal adjuvant, recent studies demonstrated that mutant LT-IIa(T34I), which exhibits no detectable binding activity by ELISA for gangliosides GD1b, GD1a, and GM1, was a very poor adjuvant. To evaluate whether other mutant enterotoxins of LT-IIa that also exhibit diminished ganglioside-binding activities have greater adjuvant activities, BALB/c mice were immunized by the intranasal route with the surface adhesin protein AgI/II of Streptococcus mutans alone or in combination with LT-IIa, LT-IIa(T14S), LT-IIa(T14I), or LT-IIa(T14D). All three mutant enterotoxins potentiated strong mucosal immune responses that were equivalent to the response promulgated by wt LT-IIa. All three mutant enterotoxins augmented systemic immune response that correlated with their ganglioside-binding activities. Only LT-IIa and LT-IIa(T14S), however, enhanced expression of MHC-II and the co-stimulatory molecules CD40, CD80, and CD86 on splenic dendritic cells. LT-IIa(T14I), and LT-IIa(T14D) had extremely diminished toxicities in a mouse Y1 adrenal cell bioassay and reduced abilities to induce the accumulation of intracellular cAMP in a macrophage cell line.