title: Oral immunization with size-purified microsphere beads as a vehicle selectively induces systemic tolerance and sensitization.
abstract: Oral administration of antigens has long been recognized as a method to prevent or delay the onset of diseases associated with untoward immune responses to self and non-self antigens. Although oral administration of antigens offers a convenient way to induce systemic tolerance, its therapeutic potential has been seriously limited by the fact that it requires repeated feeding of a large amount of antigens and that it may deteriorate ongoing autoimmune diseases when autoantigens are employed. We have previously shown that orally administered poly-D,L-lactic acid (PDLLA) microspheres containing an antigen were selectively distributed to Peyer's patches (PP) and systemic lymphoid tissues according to their diameter and then released the antigen over a long period of time. We now report that a single dose of intragastric immunization with a PDLLA microsphere 7-10 micrometer in diameter and containing 2 mg of OVA was as effective as 100 mg of water soluble OVA to suppress OVA-specific IgG and DTH response. This was associated with a large increase of Interferon-gamma production by PPT cells stimulated with an antigen and a small increase in secretory IgA specific to OVA. In contrast, administration of an antigen encapsulated in microspheres 3-4 microm in diameter led to an enhanced OVA-specific IgG response and no significant increase in OVA-specific secretory IgA. Thus, by utilizing microspheres of an appropriate diameter as a vaccination vehicle, we were able to selectively induce both systemic tolerance and sensitization by oral ingestion of single low dose of an antigen.
authors.affiliation: Division of Clinical Bio-regulatory Science, Kyoto University, Kyoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: Y
authors.initials: Y
authors.lastname: Wakatsuki
authors.forename: Y
authors.initials: Y
authors.lastname: Tabata
authors.forename: H
authors.initials: H
authors.lastname: Kawasaki
authors.forename: T
authors.initials: T
authors.lastname: Usui
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Itoh
authors.forename: S
authors.initials: S
authors.lastname: Habu
authors.forename: T
authors.initials: T
authors.lastname: Kita
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D006968:Hypersensitivity, Delayed; D007108:Immune Tolerance; D007114:Immunization; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D019344:Lactic Acid / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008863:Microspheres; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010316:Particle Size; D010581:Peyer's Patches / Q000276:immunology; D011091:Polyesters; D011108:Polymers / Q000008:administration & dosage*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013154:Spleen / Q000276:immunology
chemical_list: D000941:Antigens; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D011091:Polyesters; D011108:Polymers; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D019344:Lactic Acid; C033616:poly(lactide); D007371:Interferon-gamma; D010047:Ovalbumin