ORAL-ADMINISTRATION OF POLYMER-GRAFTED STARCH MICROPARTICLES ACTIVATES GUT-ASSOCIATED LYMPHOCYTES AND PRIMES MICE FOR A SUBSEQUENT SYSTEMICANTIGEN CHALLENGE

The mucosal ans systemic humoral immune systems can function essential ly independent of each other, responding to mucosal and parenteral ant igens, respectively. Nevertheless, antigen administered by one route c an modify responsiveness to subsequent immunization by an alternate ro ute. Here we demonstrated, in mice, in addition to stimulating rapid a nd robust sera antibody responses, intragastric (i.g.) immunization wi th human serum albumin (HSA)-containing starch microparticles (MP) gra fted with 3-(triethoxysilyl)-propyl-terminated polydimethylsiloxane (T S-PDMS) primed for enhanced specific sera IgG following a parenteral a ntigen boost. After as little as one i.g. immunization with microentra pped, but not with soluble, HSA antigen-specific proliferation and ant ibody secretion were detected in Peyer's patches (PP); this activity p eaked after three i.g. MP immunizations. We observed a progressive dis semination of antigen-specific lymphocyte reactivity from PP to spleni c tissue following oral MP immunization. Similarly, we observed a shif t in HSA-specific antibody-secreting cells from PP and mesenteric lymp h nodes to splenic tissue following i.g. MP immunization. We also demo nstrated that oral immunization with microentrapped, but not with solu ble HSA, resulted in enhanced numbers of spontaneous TH2-cytokine secr eting lymphocytes which disseminated from mucosal to systemic lymphoid compartments. This observation coincided with our findings that HSA-s pecific sers IgG1 responses in animals given HSA in MP were significan tly higher than those detected in the sera of mice given soluble HSA i .g., both before and after parenteral antigen challenge. These finding s suggest that orally-administered TS-PDMS-grafted MP, by stimulating elements of the mucosal immune system, are a valuable addition to muco sal and systemic vaccine delivery systems. (C) 1998 Elsevier Science L td. All rights reserved.