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Interbilayer-crosslinked multilamellar vesicles: Engineering lipid vesicle nanostructure for enhanced drug and vaccine delivery (invited presentation)

D. Irvine
Massachusetts Institute of Technology, US

Keywords: lipid vesicle nanostructure, drug delivery

Abstract:

New materials for vaccine delivery will be described, employing a novel class of nanoparticle drug carriers, dubbed interbilayer-crosslinked multilamellar vesicles (ICMVs). These lipid-based capsules are formed by synthesizing multilamellar liposomes, stabilized by the introduction of covalent crosslinks connecting tightly stacked lipids bilayer-to-bilayer within the vesicle walls. We show how these capsules enable the efficient loading and retention of both hydrophilic protein antigens (in the aqueous core) and lipophilic molecular adjuvants (in the vesicle walls). By sequestering both adjuvant and antigen molecules within the particle structure in this way, we found that these lipid particles form an extremely potent vaccine for both humoral and cellular immunity, eliciting up to ~30% antigen-specific CD8+ T-cells for a single epitope and strong IgG responses in mice. Notably, unlike live vaccine vectors that often must be used in so-called “heterologous” prime-boosting regimens due to anti-vector immunity, this nanoparticle vaccine could be repeatedly administered, boosting both CD8+ T-cell and antibody responses on each immunization. Implications of this strategy for obtaining strong combined T-cell and antibody responses from subunit vaccines will be discussed.
 
 
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