Whole Cholera Toxin and B Subunit Act Synergistically as an Adjuvant for the Mucosal Immune Response of Mice to Keyhole Limpet Haemocyanin

Abstract

Cholera toxin (CT) is a potent stimulator of IgA responses when adtninistered orally and has been shown to promote IgA responses to a second protein such as keyhole limpet haemocyanin (KLH) if this is fed simultaneously. ln this paper we show that whilst feeding 5 mg KLH with either 0.5 μg CT or 10 μg B subunit fails to stimulate a mucosal IgA response to KLH, feeding 0.5μg CT and 10 μg B subunit together with 5 mg KLH produces a local IgA anti-KLH response as greal as that produced by 10 μg of whole CT. ln addition to stimulating IgA responses in the lamina propria, preliminary results indicate that cellular responses are also stimulated, as we have demonstrated KLH antigen-driven proliferation of cells isolated from groups of mice fed either 10 μg CT + 5 mg KLH or O.5 μg CT + 10 μg CTB + 5 mg KLH but not mice fed KLH alone or with either 10 μg CTB or O.5 μg CT. These results indicate that the mucosal adjuvant action of CT is due to a synergistic effect involving both the GMl binding of the B subunit and adenylate cyelase activation by the A subunit.