Vaccines based on recombinant proteins avoid the toxicity and antivector immunity associated with live vaccine (for example, viral) vectors, but their immunogenicity is poor, particularly for CD8+ T-cell responses. Synthetic particles carrying antigens and adjuvant molecules have been developed to enhance subunit vaccines, but in general these materials have failed to elicit CD8+ T-cell responses comparable to those for live vectors in preclinical animal models. Here, we describe interbilayer-crosslinked multilamellar vesicles formed by crosslinking headgroups of adjacent lipid bilayers within multilamellar vesicles. Interbilayer-crosslinked vesicles stably entrapped protein antigens in the vesicle core and lipid-based immunostimulatory molecules in the vesicle walls under extracellular conditions, but exhibited rapid release in the presence of endolysosomal lipases. We found that these antigen/adjuvant-carrying vesicles form an extremely potent whole-protein vaccine, eliciting endogenous T-cell and antibody responses comparable to those for the strongest vaccine vectors. These materials should enable a range of subunit vaccines and provide new possibilities for therapeutic protein delivery.
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This work was supported in part by the Ragon Institute of MGH, MIT and Harvard, the Gates Foundation, the Department. of Defense (contract W911NF-07-D-0004) and the National Institutes of Health (P41RR002250 and RC2GM092599). The authors would like to thank A. Yadava for providing the VMP antigen. D.J.I. is an investigator of the Howard Hughes Medical Institute.
The authors declare no competing financial interests.
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Moon, J., Suh, H., Bershteyn, A. et al. Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses. Nature Mater 10, 243–251 (2011). https://doi.org/10.1038/nmat2960
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