Enhancement of DTH Response by Cholera Toxin B Subunit Inoculated Intranasally Together with Influenza HA Vaccine

Abstract

The effects of B subunit of cholera toxin (CTB) on delayed-type hypersensitivity (DTH) response to influenza vaccine derived from influenza virus A/PR / 8/34 (PR-8, HlNl) virus were investigated in B10 mice that were immunized intranasally with both influenza vaccine and CTB. The result showed [1] that intranasal inoculation of this combination augmented DTH response to influenza vaccine, which reached its peak 6 days after inoculation, and also induced accelerated DTH response upon a second inoculation of influenza vaccine alone 4 weeks later, [2] that the cross-reactive DTH response to PR-8 vaccine was elicited by the injection of the different influenza A-type virus vaccine into the footpad of the vaccinated mice, but was not by influenza B-type virus vaccine, [3] that the DTHmediating T cells were detected selectively in the lungs of mice that received the nasal inoculation of the vaccine and CTB together, but that subcutaneous inoculation of this combination failed to induce DTH-mediating T cells in the lungs. These results, together with the previous papers (Tamura et al, Vaccine 7: 257-262; 314 -320, 1989), suggest that CTB could augment both humoral and DTH responses against influenza vaccine in the respiratory mucosal tract.

Live varicella vaccine polarizes the mucosal adjuvant action of cholera toxin or its B subunit on specific Th1‐type helper T cells with a single nasal coadministration in mice

“…In a previous study, it was shown that the mutant toxin exhibited adjuvant ability to induce cellular immunity to the Oka vaccine through Th1-type helper T cells . However, cholera toxin and its B subunit have been reported to be the main promoters of a Th2-type response to various antigens [Vajdy et al, 1993;Xu-Amano et al, 1993;Okahashi et al, 1996], except for a few antigens [Tamura et al, 1988;Kikuta et al, 1990;Bowen et al, 1994]. The Fig.…”

“…In contrast, it has been reported that cholera toxin and its B subunit trigger a Th2-type response through suppression of the Th1-type response to an antigen, but they promoted predominantly a Th1-type cell response to the vaccine with a single administration. Although a few investigators have shown that cholera toxin and its B subunit evoke predominantly a mucosal adjuvant action related to Th1-type cells [Tamura et al, 1988;Kikuta et al, 1990;Bowen et al, 1994], the Oka vaccine changed the activation balance of Th1/Th2-type T cells by cholera toxin and its B subunit to the Th1-type side.…”

“…The heat-labile enterotoxin induces both Th1-and Th2-type helper T-cell responses to an antigen, but the former response predominates on exposure to the Oka vaccine Kamiya et al, 2001]. It has been reported that cholera toxin and its B subunit also induce both Th1-and Th2-type helper T-cell responses to some antigens [Tamura et al, 1988;Kikuta et al, 1990;Xu-Amano et al, 1993;Hornquist and Lycke, 1993;Bowen et al, 1994]. Cholera toxin and its B subunit suppress the Th1-type response to antigens and induce predominantly a specific Th2-type cell response instead [Vajdy et al, 1993;Xu-Amano et al, 1993;Okahashi et al, 1996;Gagliardi et al, 2000].…”

Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin.

“…Work by Shen et al (245), for example, made use of the receptor specificity of CT to demonstrate that glycolipids inserted into lipid vesicles retained their biological function and orientation, showing by gel ifitration that labeled CT coeluted with a GM1-containing vesicle-rich fraction. Other uses include studies of immune system stimulation (6,114,157), nuclear magnetic resonance or HPLC studies of antibody diversity and antibody-antigen interactions (8,172,259), and studies of vaccine development, in which it is used as a model (216). Hybrid proteins consisting of B subunit and foreign antigens for immunoprotection have generated some recent interest (42).…”