Relative to soluble antigen, particulate antigen is much better recognized by the immune system as being foreign and leads to an altered way of uptake, processing and presentation by antigen presenting cells. However, a general strategy to formulate protein antigens into nanoparticles that are sufficiently small to efficiently drain to the lymph nodes is still lacking. Here we present a bio-conjugation approach involving covalent coupling of stimuli (i.e. temperature and pH) responsive polymers to a protein antigen. These stimuli responsive properties affords straightforward polymer-protein conjugation below in aqueous medium below the polymer phase transition temperature, whereas above this phase transition temperature nanoparticles are formed. We report on an interesting class of pH-degradable temperature-responsive polymers that at fixed temperature undergo an irreversible hydrophobic to hydrophilic transition. This unique property causes disassembly of the nanoparticles, liberating the protein for further processing. We report on how the polymer-protein nanoparticles interact with dendritic cells (i.e. the most potent class of antigen presenting cells) and how they alter the antigen-specific immune response.

Multiresponsive polymer-protein conjugates as immuno-modulating stategy

249th National Meeting (2015)

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