Strategies that allow modulating proteins between soluble and particulate state are of great interest for the design of the next generation of vaccines. Indeed, particulate protein antigens are much better recognized by the immune systems as being foreign, leading to an altered route of cellular uptake, antigen processing and presentation. Importantly, this leads to strongly enhanced cellular immune responses that are crucial to confer protective immunity against intracellular pathogens such as HIV, tuberculosis, malaria etc� and for anti-cancer vaccines that prevent tumor growth and metastasis. Here we report on an novel class of dual temperature- and pH-responsive polymers for protein-conjugation, synthesized via RAFT. Via a smart combination of temperature-responsive and pH-degradable monomers the cloud point temperature (CPT) of the resulting copolymers can be tailored to any desired temperature below physiological or room temperature. Using a functional RAFT CTA, these copolymers and block copolymers can be conjugated to proteins. Soluble polymer-protein conjugates are formed below the CPT of the polymer whereas self-assembled nanoparticles form above the CPT. In acidic medium (i.e. simulated endo/lysosomal conditions at a pH of 4 to 4) the polymer hydrolyzes into fully soluble unimers, accompanied by disassembly of the polymer-protein nanoparticles. The potential of these polymer-protein conjugates for vaccine delivery is subsequently assessed in vitro dendritic cell and T cell models.

Dual temperature- and pH-responsive polymers for protein conjugation and vaccine design

246th National Meeting (2013)

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