Influence of polymer hydrolysis on adjuvant effect of Gantrez®AN nanoparticles: Implications for oral vaccination

The adjuvant effect of methylvinylether-co-maleic anhydride (Gantrez®AN) nanoparticles was investigated during oral vaccination of mice with F4 adhesins of F4-positive Escherichia coli. To differentiate whether the adjuvant effect originated from a nanoparticle effect or a polymer effect, 20 μg F4 was administered as slightly crosslinked F4-containing nanoparticles (g(F4)0.01) or as F4 mixed with slightly crosslinked pure nanoparticles (F4 + g0.01).The F4-specific immune response was reduced using F4-containing nanoparticles due to complete shielding of F4, whereas oral administration of F4 + g0.01 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 + g0.01 was lost due to an altered polymer reactivity caused by partial hydrolysis of anhydride groups of Gantrez®AN. Combining F4 with nanoparticles stabilised with a higher crosslinker amount during nanoparticle synthesis (F4 + g0.22) could overcome the effect of partial polymer hydrolysis, as higher levels of ASC were detected. Hence, an in-depth characterisation of the Gantrez®AN polymer is required as stability issues can alter its biological effect during oral vaccination.

Graphical abstractPartial hydrolysis of the anhydride groups of methylvinylether-co-maleic anhydride (Gantrez AN) reduced its adjuvant effect during oral vaccination of mice with F4-adhesins of Escherichia coli, formulated in nanoparticles. A higher degree of crosslinking during nanoparticle synthesis could overcome this negative effect of partial polymer hydrolysis.Figure optionsDownload full-size imageDownload as PowerPoint slide