title: Distinctive immunomodulatory and inflammatory properties of the Escherichia coli type II heat-labile enterotoxin LT-IIa and its B pentamer following intradermal administration.
abstract: The type I and type II heat-labile enterotoxins (LT-I and LT-II) are strong mucosal adjuvants when they are coadministered with soluble antigens. Nonetheless, data on the parenteral adjuvant activities of LT-II are still limited. Particularly, no previous study has evaluated the adjuvant effects and induced inflammatory reactions of LT-II holotoxins or their B pentameric subunits after delivery via the intradermal (i.d.) route to mice. In the present report, the adjuvant and local skin inflammatory effects of LT-IIa and its B subunit pentamer (LT-IIaB(5)) were determined. When coadministered with ovalbumin (OVA), LT-IIa and, to a lesser extent, LT-IIaB(5) exhibited serum IgG adjuvant effects. In addition, LT-IIa but not LT-IIaB(5) induced T cell-specific anti-OVA responses, particularly in respect to induction of antigen-specific cytotoxic CD8(+) T cell responses. LT-IIa and LT-IIaB(5) induced differential tissue permeability and local inflammatory reactions after i.d. injection. Of particular interest was the reduced or complete lack of local reactions, such as edema and tissue induration, in mice i.d. inoculated with LT-IIa and LT-IIaB(5,) respectively, compared with mice immunized with LT-I. In conclusion, the present results show that LT-IIa and, to a lesser extent, LT-IIaB(5) exert adjuvant effects when they are delivered via the i.d. route. In addition, the low inflammatory effects of LT-IIa and LT-IIaB(5) in comparison to those of LT-I support the usefulness of LT-IIa and LT-IIaB(5) as parenterally delivered vaccine adjuvants.
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo SP 05508-000, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Mathias-Santos
authors.forename: Juliana F
authors.initials: JF
authors.lastname: Rodrigues
authors.forename: Maria Elisabete
authors.initials: ME
authors.lastname: Sbrogio-Almeida
authors.forename: Terry D
authors.initials: TD
authors.lastname: Connell
authors.forename: Luís C S
authors.initials: LC
authors.lastname: Ferreira
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000276:immunology* / Q000633:toxicity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004768:Enterotoxins / Q000008:administration & dosage* / Q000276:immunology* / Q000633:toxicity; D029968:Escherichia coli Proteins / Q000008:administration & dosage* / Q000276:immunology* / Q000633:toxicity; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000473:pathology; D007271:Injections, Intradermal; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012867:Skin / Q000187:drug effects* / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007074:Immunoglobulin G; D010047:Ovalbumin; C027538:heat-labile enterotoxin, E coli