Vaccine delivery: where polymer chemistry meets immunology.

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Vaccines are among the most important innovations in human history. The development and widespread implementation of vaccines over the past two centuries have saved billions of lives and have completely eliminated or dramatically reduced the global burden of diseases such as smallpox, polio and diphtheria. However, there remains an urgent and unmet need for vaccines against many diseases that have proven recalcitrant to traditional immunization approaches such as malaria, tuberculosis and HIV, which are collectively responsible for over 4.5 million deaths per year [1]. This challenge persists because vaccines, which have historically been based on killed or weakened forms of a microbe (e.g., virus or bacterium), often fail to elicit the correct type or magnitude of immune response to confer protective immunity. The need to achieve greater control over the magnitude and phenotype of an immune response has catalyzed a shift away from empirical vaccinology toward the rational design of vaccines founded upon a fundamental understanding of how the immune system combats infection. Toward this end, many modern vaccines combine recombinant protein antigens – to define the antigenspecificity of the response – with synthetic immunostimulatory molecules (adjuvants) that engage specific pattern recognition receptors (PRRs) – to generate an appropriate innate immune response to initiate and shape the adaptive response to the antigen. For example, the Cervarix human papillomavirus vaccine contains both recombinant virus like particles and monophosphoryl lipid A, an agonist of TLR-4 [2]. However, this shift toward developing successful synthetic vaccines is associated with several important drug delivery challenges. How can vaccines be delivered to the proper antigen presenting cells? How can vaccines be delivered to the proper pathways within these cell populations? How can vaccines be enriched within lymph nodes – the command centers of an immune response – while minimizing systemic distribution and the risk of potential adverse side effects? How can physicochemically diverse vaccine constituents be packaged and delivered to generate an optimal response? Polymeric delivery systems enable solutions to many of these challenges, and recent advances in polymer chemistry are poised to impact the future of vaccine delivery.