Influence of polymer hydrolysis on adjuvant effect of Gantrez (R) AN nanoparticles: Implications for oral vaccination

Abstract

The adjuvant effect of methylvinylether-co-maleic anhydride (Gantrez (R) AN) nanoparticles was investigated during oral vaccination of mice with F4 adhesins of F4-positive Escherichia coil. To differentiate whether the adjuvant effect originated from a nanoparticle effect or a polymer effect, 20 jig F4 was administered as slightly crosslinked F4-containing nanoparticles (g(F4)(0.01)) or as F4 mixed with slightly crosslinked pure nanoparticles (F4 + g(0.01)). The F4-specific immune response was reduced using F4-containing nanoparticles due to complete shielding of F4, whereas oral administration of F4 + g(0.01) increased the level of F4-specific antibody-secreting cells (ASC) in the spleen. When repeating the vaccination study after 6 months using freshly prepared nanoparticles, the adjuvant effect of F4 + g(0.01) was lost due to an altered polymer reactivity caused by partial hydrolysis of anhydride groups of Gantreze (R) AN. Combining F4 with nanoparticles stabilised with a higher crosslinker amount during nanoparticle synthesis (F4 + g(0.22)) could overcome the effect of partial polymer hydrolysis, as higher levels of ASC were detected. Hence, an in-depth characterisation of the GantrezeAN polymer is required as stability issues can alter its biological effect during oral vaccination. (C) 2011 Published by Elsevier B.V.