title: Oral administration of polymer-grafted starch microparticles activates gut-associated lymphocytes and primes mice for a subsequent systemic antigen challenge.
abstract: The mucosal and systemic humoral immune systems can function essentially independent of each other, responding to mucosal and parenteral antigens, respectively. Nevertheless, antigen administered by one route can modify responsiveness to subsequent immunization by an alternate route. Here we demonstrated, in mice, in addition to stimulating rapid and robust sera antibody responses, intragastric (i.g.) immunization with human serum albumin (HSA)-containing starch microparticles (MP) grafted with 3-(triethoxysilyl)-propyl-terminated polydimethylsiloxane (TS-PDMS) primed for enhanced specific sera IgG following a parenteral antigen boost. After as little as one i.g. immunization with microentrapped, but not with soluble, HSA antigen-specific proliferation and antibody secretion were detected in Peyer's patches (PP); this activity peaked after three i.g. MP immunizations. We observed a progressive dissemination of antigen-specific lymphocyte reactivity from PP to splenic tissue following oral MP immunization. Similarly, we observed a shift in HSA-specific antibody-secreting cells from PP and mesenteric lymph nodes to splenic tissue following i.g. MP immunization. We also demonstrated that oral immunization with microentrapped, but not with soluble HSA, resulted in enhanced numbers of spontaneous Th2-cytokine secreting lymphocytes which disseminated from mucosal to systemic lymphoid compartments. This observation coincided with our findings that HSA-specific sera IgG1 responses in animals given HSA in MP were significantly higher than those detected in the sera of mice given soluble HSA i.g., both before and after parenteral antigen challenge. These findings suggest that orally-administered TS-PDMS-grafted MP, by stimulating elements of the mucosal immune system, are a valuable addition to mucosal and systemic vaccine delivery systems.
authors.affiliation: Department of Pathology, McMaster University, Hamilton, Ont., Canada.
authors.forename: P L
authors.initials: PL
authors.lastname: Heritage
authors.forename: B J
authors.initials: BJ
authors.lastname: Underdown
authors.forename: M A
authors.initials: MA
authors.lastname: Brook
authors.forename: M R
authors.initials: MR
authors.lastname: McDermott
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004129:Dimethylpolysiloxanes; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology*; D006801:Humans; D007114:Immunization / Q000379:methods*; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008214:Lymphocytes / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D012709:Serum Albumin / Q000008:administration & dosage* / Q000276:immunology; D012828:Silicones; D013213:Starch
chemical_list: D004129:Dimethylpolysiloxanes; D004337:Drug Carriers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D012709:Serum Albumin; D012828:Silicones; D013213:Starch