Immunostimulatory sequence oligdeoxynucleotide/cholera toxin B conjugate: a novel allergen-independent intranasal vaccine for allergic rhinitis

Abstract

Recent studies have shown that by acting as strong TH1 response-inducing adjuvants, DNA immunostimulatory sequence oligdeoxynucleotides (ISS-ODNs) can be used in the treatment of allergic diseases, and efforts are being made to enhance these TH1 adjuvant actions. To determine whether intranasally delivered ISS-ODN/cholera toxin B (CTB) conjugate has enhanced antiallergic effects in an allergic rhinitis mouse model. BALB-c mice were sensitized with ovalbumin. Chemical conjugation of ISS-ODN and CTB was performed. After a single local intranasal administration of 50 microg of ISS-ODN or high- and low-dose (50- and 5-microg) ISS-ODN/CTB conjugate, we measured the allergic response in terms of sneezing events, eosinophil infiltration in the nasal mucosa, serum ovalbumin specific IgE and IgG2a levels, and TH1 and TH2 cytokine levels in nasal lavage fluid and spleen cell cultures. A single local administration of 50 microg of ISS-ODN did not suppress the allergic phenotype. However, 50 and 5 microg of ISS-ODN/CTB conjugate significantly attenuated allergic symptoms, eosinophil infiltration in the nasal mucosa, and interleukin 4 production from nasal lavage fluid and cultured splenocyte supernatant compared with the allergic control. Serum specific IgG2a and interleukin 12 production in nasal lavage fluid and spleen cell cultures was significantly increased. In a mouse model of allergic rhinitis, a single intranasal delivery of low-dose ISS-ODN/CTB conjugate effectively protects previously sensitized mice from allergic hypersensitivity responses. With further research, ISS-ODN/CTB conjugate may serve as a new allergen-independent intranasal vaccine for the treatment of allergic rhinitis.