Prolonged oral treatment with low doses of allergen conjugated to cholera toxin B subunit suppresses immunoglobulin E antibody responses in sensitized mice.

BACKGROUND: Oral tolerance is a long recognized method for inducing systemic immunological tolerance. However, large doses of antigen and frequent administrations are often required. By linking the antigen to the nontoxic mucosa-binding B subunit of cholera toxin (CTB), the required amount can be dramatically reduced. We have previously shown that mucosal administration of small amounts of antigens coupled to CTB can suppress peripheral Th1 cell-reactivity and associated inflammatory immunopathology in both naive and systemically-immunized animals. Induction of oral tolerance by repeated feeding of relatively small doses of antigen has, in some cases been shown to involve the generation of regulatory Th2-like CD4+ T cells, and hence could promote rather than suppress type I immunoglobulin (Ig) E-mediated allergic responses.

OBJECTIVES: We examined whether oral prophylactic or therapeutic administration of a model allergen coupled to CTB would modulate allergen-specific IgE responses in high IgE responder Balb/c mice.

METHODS: Ovalbumin (OVA) was used as a model allergen. Mice were treated perorally with free or CTB-coupled OVA before or after systemic priming with alum-adsorbed OVA. Allergen-specific IgE levels in serum were measured with the passive cutaneous anaphylaxis test at various time-points.

RESULTS: Oral administration of a single low dose of CTB-linked OVA, prior to systemic sensitization and challenge with OVA, suppressed allergen-specific serum IgE antibody responses. Treatment with comparable doses of free OVA was much less effective. Most importantly, oral treatment with CTB-OVA conjugate could also suppress an already initiated IgE antibody response, but to achieve such a 'therapeutic effect', administration of multiple low doses of conjugate over a long time was required. Oral treatment with CTB-OVA conjugate could also effectively suppress antigen-specific Th1-mediated delayed-type hypersensitivity. Thus treatment with a CTB-conjugated model allergen can affect a broad range of T-cell-driven immune responses, even in antigen-experienced animals.

CONCLUSION: These results may impact on the development of therapeutic vaccines against type I allergies.