Induction of secretory and serum antibody responses following oral administration of antigen with bioadhesive degradable starch microparticles.

Abstract

Bioadhesive degradable starch microparticles were used to deliver antigen and immunoglobulin A (IgA)-enhancing cytokines to the oral mucosa. Degradable starch microparticle immunization groups consisted of rats dosed topically at the sublingual epithelium of the oral cavity, by subcutaneous injection in the vicinity of the major salivary glands or by oral intubation with degradable starch microparticles containing dinitrophenyl-bovine serum albumin +/- IL-5/IL-6 +/- penetration enhancer (alpha-lysophosphatidylcholine). Dinitrophenyl-bovine serum albumin was also adsorbed onto alum for salivary gland vicinity injection and administered to the oral cavity in soluble form. Animals were subjected to 3 immunization cycles, and sequential samples were assayed by radioimmunoassay for salivary IgA, tear IgA and serum IgG anti-dinitrophenyl antibodies after secondary and tertiary immunization. Salivary IgA responses were highest in degradable starch microparticle groups receiving penetration enhancer at 71 days post-secondary immunization and continued in one degradable starch microparticle((oral cavity) and two injected (salivary gland vicinity) groups for up to 88 days post-tertiary immunization. Long-term tear responses were also observed in degradable starch microparticle groups receiving penetration enhancer, but they dissipated before the salivary gland-alum responses following tertiary immunization. Serum IgG responses were most pronounced in salivary gland groups, but long-term low level responses were detectable in oral cavity groups receiving degradable starch microparticle formulations with penetration enhancer. Inclusion of IL-5 and IL-6 in oral cavity-delivered degradable starch microparticle formulations consistently enhanced tear IgA while only upregulating salivary IgA antibody responses at early time points post immunization. IL-5 and IL-6 did not enhance serum IgG antibodies in any group. These data indicate that bioadhesive degradable starch microparticles can be used as a vehicle to deliver antigen and cytokine signals to the oral cavity and, when delivered in combination with a penetration enhancer, can potentiate long-term salivary IgA responses.