Oral Adjuvant Therapy in the Development of Immunological Protection Against Mucosal Pathogens.
Abstract
Here we report the development of a non-toxic adjuvant for orally administered antigens that can elicit the production of both serum IgG and mucosal IgA against antigens with which it is delivered. This adjuvant is a mutant form of the heat-labile cholera-like toxin of E. coli. This adjuvant, designated L/T(Rl92G), acts as a mucosal adjuvant, increasing the serum IgG and mucosal IgA responses to co-administered antigen beyond that achieved with administration of antigen alone. Further, L/T(Rl92G) prevented the induction of tolerance to antigen and did not induce tolerance against itself as demonstrated by the presence of significant serum anti-LT IgG and mucosal anti-LT IgA antibodies in immunized mice. In addition to its potential use as an adjuvant for unrelated antigens, use of this non-toxic adjuvant as one component of a whole-cell/toxoid vaccine against cholera-related enteropathies should provide more epitopes for induction of neutralizing antibodies as well as adjuvant activity not associated with B subunit alone. In addition, this mutant LT provides for the first time a model system in which to examine the role of proteolytic processing with respect to the enterotoxic and immunologic properties of ADP-ribosylating toxins both in vitro and in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1995
- Accession Number
- ADA302243
Entities
People
- John D. Clements
Organizations
- Tulane University of Louisiana