Recent studies have demonstrated that systemic and mucosal administrat
ion of soluble antigens in biodegradable microparticles can potentiate
antigen-specific humoral and cellular immune responses. However, curr
ent microparticle formulations are not adequate for all vaccine antige
ns, necessitating the further development of microparticle carrier sys
tems. In this study, we developed a novel microparticle fabrication te
chnique in which human serum albumin (HSA) was entrapped in starch mic
roparticles grafted with 3-(triethoxysilyl)-propyl-terminated polydime
thylsiloxane (TS-PDMS), a biocompatible silicone polymer. The immunoge
nicity of HSA was preserved during the microparticle fabrication proce
ss. Following intraperitoneal immunization of mice, TS-PDMS-grafted mi
croparticles (MP) dramatically enhanced serum IgG responses compared w
ith ungrafted MP and soluble HSA alone (P < 0.001). When delivered ora
lly, both TS-PDMS-grafted and ungrafted microparticles elicited HSA-sp
ecific IgA responses in gut secretions, in contrast to orally administ
ered soluble antigen. Indeed, TS-PDMS-grafted microparticles stimulate
d significantly stronger serum IgG (P < 0.005) and IgA (P < 0.001) res
ponses compared with those elicited by ungrafted microparticles. These
findings indicate that TS-PDMS-grafted starch microparticles have pot
ential as systemic and mucosal vaccine delivery vehicles.