Structure-based programming of lymph-node targeting in molecular vaccines
Author(s)Liu, Haipeng; Moynihan, Kelly Dare; Zheng, Yiran; Szeto, Gregory Lee; Li, Adrienne Victoria; Huang, Bonnie; Van Egeren, Debra S.; Irvine, Darrell J.; Lui, Haipeng; Park, Clara, S.M. Massachusetts Institute of Technology; ... Show more Show less
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In cancer patients, visual identification of sentinel lymph nodes (LNs) is achieved by the injection of dyes that bind avidly to endogenous albumin, targeting these compounds to LNs, where they are efficiently filtered by resident phagocytes1, 2. Here we translate this ‘albumin hitchhiking’ approach to molecular vaccines, through the synthesis of amphiphiles (amph-vaccines) comprising an antigen or adjuvant cargo linked to a lipophilic albumin-binding tail by a solubility-promoting polar polymer chain. Administration of structurally optimized CpG-DNA/peptide amph-vaccines in mice resulted in marked increases in LN accumulation and decreased systemic dissemination relative to their parent compounds, leading to 30-fold increases in T-cell priming and enhanced anti-tumour efficacy while greatly reducing systemic toxicity. Amph-vaccines provide a simple, broadly applicable strategy to simultaneously increase the potency and safety of subunit vaccines.
DepartmentMassachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Materials Science and Engineering; Ragon Institute of MGH, MIT and Harvard; Koch Institute for Integrative Cancer Research at MIT
Nature Publishing Group
Liu, Haipeng, Kelly D. Moynihan, Yiran Zheng, Gregory L. Szeto, Adrienne V. Li, Bonnie Huang, Debra S. Van Egeren, Clara Park, and Darrell J. Irvine. “Structure-Based Programming of Lymph-Node Targeting in Molecular Vaccines.” Nature 507, no. 7493 (February 16, 2014): 519–522.
Author's final manuscript