Nanoparticles are of great interest in vaccine delivery, due to their ability to mimic the structure of pathogens and rapidly transport antigen and immunostimulatory adjuvant molecules from injection sites through lymphatics to lymph nodes.  To achieve well-defined nanoparticles with precision-engineered properties, we explored the design of well-defined block copolymer amphiphiles with the general structure lipid-oligonucleotide-cargo, which self-assemble into micelles with tunable stability determined by the presence of a G-quartet-forming guanine oligonucleotide repeat block.  On injection in vivo, these micelles enter lymphatics efficiently, but disassemble into unimers on reaching lymph nodes, with lipid tails of the amphiphiles inserting in cell membranes, sequestering vaccine cargo in the node.  By optimizing the stability of micelles to maximize capture in the lymph node, immune responses to peptide and protein vaccines can be dramatically enhanced.  Application of this approach to enhanced vaccines for infectious disease and strategies for tumor immunotherapy will be discussed.

Dynamically stabilized oligonucleotide and peptide micelles for lymphoid tissue targeting: Designing vaccines one molecule at a time

244th National Meeting (2012)

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