Structure-based Programming of Lymph Node Targeting in Molecular Vaccines
By Haipeng Liu, K. Moynihan, Yiran Zheng, G. Szeto, Adrienne V. Li, Bonnie Huang, Debra Van Egeren, Clara Park, D. Irvine. Nature, 2014
864 citations recorded by the source corpus.
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 phagocytes. 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.
Subfields: Immunology, Molecular Biology, Radiology, Nuclear Medicine and Imaging
View Paper: https://www.semanticscholar.org/paper/fc50799cadac857a479adb1f71461e3c59df9ac0
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Citations in the corpus
- Control of Polymeric Nanoparticle Size to Improve Therapeutic Delivery (2015, background): “recently demonstrated the importance of this phenomena in forming amphipathic micelles (15 – 20 nm) through conjugating protein antigen or adjuvant to a lipid moiety [70].”
- Vaccine adjuvants: mechanisms and platforms (2023, background): “Experimental results showed that the vaccine bound albumins and accumulated heavily in lymph nodes, leading to a 30-fold increase in T-cell production and significantly enhanced anti-tumor efficacy after injection in mice.(113) Another example is 1,2-distearoyl-sn-glycero3-phosphoethanolamine (DSPE)”
- Concepts of nanoparticle cellular uptake, intracellular trafficking, and kinetics in nanomedicine. (2019, background): “phiphilic compounds with lipophilic domains can adhere to circulating albumin which is then efficiently transported to lymph nodes [294].”