Impact of Toxin-Specific Antibodies on the Adjuvanticity and Inflammatory Effects Induced by Parenterally Administered Escherichia coli heat-Labile Toxin

Abstract

Introduction: Heat-labile toxins (LT), produced by enterotoxigenic Escherichia coli (ETEC) strains, exert potent adjuvant effects when admixed or linked to antigens delivered via mucosal, transcutaneous or parenteral routes. There is limited information regarding the impact of preexisting immunity on the immunomodulatory properties of LT, which is frequently observed among people infected with ETEC. Aims: In the present study, we evaluated the effect of anti-LT antibodies on the adjuvant and inflammatory activities triggered by LT admixed with a specific vaccine antigen following subcutaneous administration to mice. Material and Methods/Results: Animals were immunized with dengue virus nonstructural protein (NS1), as model antigen, in combination with native LT in the presence of LT-specific antibodies. Exposure to anti-LT antibodies did not impair the humoral adjuvanticity of LT regarding to the magnitude of the serum anti-NS1 IgG titers. In addition, anti-toxin antibodies did not reduce neutrophil migration nor edema formation after s.c. administration of LT. Nonetheless, administration of LT admixed with anti-LT antibodies changed the local cytokine production profile and modulated the NS1specific T cell responses to a Th1-type pattern. Conclusion: These results indicate that preexisting immunity does not affect the humoral adjuvant activities but may modulate different aspects of both innate and adaptive immune responses induced by parenterally administered LT.