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

Abstract

This study was undertaken to determine whether the specific Th1- or Th2-cell response to varicella-zoster virus was induced predominantly by a mucosal adjuvant, cholera toxin, in mice. A commercially available live varicella vaccine (Oka strain) and cholera toxin or its B subunit were administered simultaneously via the nasal route. Delayed-type hypersensitivity to the Oka vaccine was induced, but the systemic neutralizing antibody response was low. The delayed-type hypersensitivity evoked after a single administration was relatively higher than that on administration three times. When spleen cells from mice immunized once with the vaccine and cholera toxin or its B subunit were restimulated with the live vaccine in vitro, there was greater thymidine uptake and production of interleukin- 2 (IL-2) than controls, but only a low level of IL-4 production. The production of IL-2 induced by the B subunit of cholera toxin was less than that by cholera toxin and a mutant of Escherichia coli enterotoxin on co-immunization with the vaccine in mice. Cholera toxin and its B subunit have been reported to induce predominantly a specific Th2-type T-cell response to various antigens. However, the Oka vaccine is an antigen that polarizes the activation of specific Th1/Th2-type T cells by cholera toxin or its B subunit to the Th1-type side. Cholera toxin and its B subunit are thus useful mucosal adjuvants for inducing cellular immunity to the Oka vaccine similar to Escherichia coli enterotoxin.

Cholera Toxin B-Subunit Gene Enhances Mucosal Immunoglobulin A, Th1-Type, and CD8+Cytotoxic Responses When Coadministered Intradermally with a DNA Vaccine

“…Our observations are in agreement with those from recent work in which coadministration of CtB onto skin favored the development of a vigorous Th1 cellular response (1), while the CT holotoxin was associated with the induction of a Th2-type response (13,43). Nevertheless, more recent findings propose that Th1-Th2 polarization may depend not only on the adjuvant but also on the antigen coadministered (36). Consistent with this, administration of the HPV-16 L1 antigen, in the form of VLPs, prompts both Th1 and Th2 responses in mice (28), chimpanzees (29), and humans (31).…”

Recombinant simian varicella viruses expressing respiratory syncytial virus antigens are immunogenic

“…The varicella vaccine, currently administered as one or two subcutaneous inoculations, as well as natural VZV infection, induces a Th1-biased immune response (Sasaki et al, 2003;Kamiyama et al, 2000;Phumiamorn et al, 2003;Yu et al, 2005). Intranasal VZV Oka immunization, which is also feasible, would also probably induce a mucosal Th1-mediated immune response (Bogger-Goren et al, 1982;Terada et al, 2002).…”

The Cholera Toxin as a Biotechnological Tool

“…In most cases, CT induced a Th2 bias response [Lavelle et al, 2004;Okahashi et al, 1996]. However, other studies have reported Th1 [Sasaki et al, 2003;Taniguchi et al, 2008] or mixed Th1/Th2 responses following oral, sublingual and intranasal immunization with antigens in the presence of CT [Cuburu et al, 2007;Fecek et al, 2010]. More importantly, subsequent studies showed that CT elicited a long-term memory response and thus was detectable long after the initial immune response [Soenawan et al, 2004;Vajdy and Lycke, 1992].…”