Cholera holotoxin and its B subunit enhance Peyer's patch B cell responses induced by orally administered influenza virus: Disproportionate cholera toxin enhancement of the IgA B cell response

Abstract

In these studies we analyzed the adjuvant effect of cholera holotoxin or cholera toxin (CT) B subunit on the B cell response to mucosal antigens. Purified Peyer's patch B cells obtained from mice at varying periods of time after oral administration of inactivated influenza virus, with or without a CT preparation, were stimulated in vitro in the absence or presence of various lymphokines. Responses were measured by an antigen- and isotype-specific ELISPOT assay. In this system cultures containing a combination of lymphokines [interleukin 5 (IL 5), interferon-gamma (IFN-gamma), IL 4] gave comparable responses to those containing T cells from immunized mice or supernatant of concanavalin A-stimulated T cells and therefore were assumed to express optimum or near optimum B cell responses. Administration of a CT preparation along with influenza virus increased the number of B cells producing anti-influenza antibodies of both the IgM and IgA isotypes, with the effect on the IgA response at least threefold greater than the effect on the IgM response. These results thus indicate that CT preparations enhance the memory B cells response in Peyer's patches and, in addition, suggest that CT enhances isotype switching. In this antigen-specific B cell system IL 4 augmented responses in cultures containing IL 5 but not IFN-gamma; in addition, IL 5 and IFN-gamma acted in an additive fashion. Thus, these findings suggest that the effects of IL 5 and IFN-gamma are at least in part, mediated via different cellular differentiation pathways.

Modulation of oral tolerance to ovalbumin by cholera toxin and its B subunit

“…Indeed, feeding OVA with CT primed the immune system for OVA as well and allowed a higher IgG anti-OVA response after parenteral boosting. A low systemic IgA anti-OVA response was also observed only in this group, reflecting the strong stimulation of the mucosal immune system induced by feeding CT with a second antigen, as already reported [2,6,7,111.…”

Comparison of Memory B Cell, Antibody-Secreting Cell, and Plasma Antibody Responses in Young Children, Older Children, and Adults with Infection Caused by Vibrio cholerae O1 El Tor Ogawa in Bangladesh

“…We hypothesize that these reduced responses following vaccination compared to infection may reflect the absence of the immunoadjuvantative properties of CT in current oral cholera vaccines. Experimental studies in animal models evaluating oral adjuvanticity of the toxin have demonstrated that CT stimulates a greater mucosal immune response than CtxB alone (4,6); unfortunately, the use of CT as a vaccine component is limited due to its toxicity, although mutant toxoids are being explored for their use in vaccines (28,40). The precise differences in immune stimulation between wild-type disease and current vaccines remain to be elucidated, and further studies are warranted to account for the agespecific differences in long-term vaccine efficacy seen with current vaccine formulations.…”

Cholera toxin B stimulates systemic neutralizing antibodies after intranasal co-immunization with measles virus

“…Fax +352 404238. e-mail claude.muller@santel.lu enterotoxin was found to be sufficient for a strong adjuvant effect (Chen& Strober, 1990;McKenzie & Halsey, 1984;Tamura et al, 1992). CTB is non-toxic and has been used extensively in humans as a component of a cholera vaccine (Clemens et al, 1990).…”

“…These were either mixed with CTB (Tamura et al, 1992), conjugated with cross-linking agents (McKenzie & Halsey, 1984;Menge et al, 1993) or genetically fused (Dertzbaugh et al, 1990) to the B subunit. Despite encouraging results, much less is known about the adjuvant effect of CTB in combination with viral particles (Mbawuiki & Wyde, 1993;Chen & Strober, 1990;Israel et al, 1992;Liang et al, 1988). In most studies antiviral immune responses were enhanced when viral proteins were combined with CTB or the holotoxin; e.g.…”