Structure-based programming of lymph-node targeting in molecular vaccines
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Irvine_Structure-based.pdf
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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
Date Issued
February 2014
Journal
Nature
Publisher
Nature Publishing Group
Citation
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.
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts 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
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/nature12978
