MECHANISM OF ENHANCEMENT OF THE IMMUNE-RESPONSES TO INFLUENZA VACCINEWITH CHOLERA-TOXIN B-SUBUNIT AND A TRACE AMOUNT OF HOLOTOXIN

Cholera toxin B subunit (CTB) (1 mu g) and a trace amount of cholera t oxin (CT) (0.1-10 ng), when inoculated intranasally into Balb/c mice t ogether with influenza vaccine, induced synergistically a greater dela yed-type hypersensitivity (DTH) response to the vaccine than did a tra ce amount of CT alone. In par allel with the in vivo response, normal peritoneal macrophages that were incubated in vitro with the vaccine a nd the CT-containing CTB, induced a higher adenylate cyclase activity and a greater ability to transfer DTH response into naive recipient mi ce than did the macrophages incubated with the vaccine and CT. The tre atment of macrophages with the vaccine and CTB failed to induce either adenylate cyclase or DTH response. From these results, the mechanism by which CTB and a trace amount of CT enhance immune responses synergi stically could be explained by the enhancement of the CT action on mac rophages or by the efficient binding of a trace amount of CT to antige n-presenting cells in the presence of a relatively large amount of CTB , resulting in enhanced cyclic AMP formation followed by enhanced anti gen presentation.