Starch microparticles as a vaccine adjuvant: Only uptake in Peyer's patches decides the profile of the immune response

Abstract

Starch microparticles, an effective adjuvant for oral vaccination in mice, are taken up over the follicle-associated epithelium (FAE) in Peyer's patches when human serum albumin is conjugated to the particles (HSAmp). When recombinant cholera toxin B subunit (rCTBmp) is conjugated, they are taken up over both the FAE and the villus epithelium. This study investigated the effects of the different targeting on the immune response by using particles with both HSA and rCTB (HSA/rCTBmp). The response induced after oral immunisation with this formulation in mice was compared with that obtained after administration of HSAmp, rCTBmp or both given concomitantly (HSAmp + rCTBmp) and after subcutaneous administration. Both the HSA- and rCTB-specific responses were followed quantitatively (as assessed by the anti-[IgM + IgG] level, the s-IgA response and the delayed-type hypersensitivity [DTH] response), or qualitatively (by the IgG subclass profile). After subcutaneous administration, the rCTB-specific IgM + IgG and DTH responses were lower after HSA/rCTBmp than after rCTBmp and the HSA-specific subclass ratio (IgG1/IgG2a + IgG2b) was lower with HSAmp + rCTBmp (but not with HSA/rCTBmp) compared to HSAmp. However, no quantitative and qualitative differences in the immune response after oral administration were detected when rCTB was added to HSAmp. The results indicate that only the uptake over the Peyer's patches decides the immune responses after oral administration and that the increased targeting to GM1 receptors of the villus epithelium does not affect the immune response. Moreover, the qualitative Th1/Th2-balance is controlled by the inherent properties of the antigens in the microparticles upon subcutaneous administration. Thus, the obtained information is important for designing oral microparticulate vaccines in order to obtain the wanted immune response.