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Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses
Open accessAbstract
Vaccines based on recombinant proteins avoid toxicity and anti-vector immunity associated with live vaccine (e.g., viral) vectors, but their immunogenicity is poor, particularly for CD8+ T-cell (CD8T) responses. Synthetic particles carrying antigens and adjuvant molecules have been developed to enhance subunit vaccines, but in general these materials have failed to elicit CD8T responses comparable to live vectors in preclinical animal models. Here, we describe interbilayer-crosslinked multilamellar vesicles (ICMVs) formed by crosslinking headgroups of adjacent lipid bilayers within multilamellar vesicles. ICMVs 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 ICMVs form an extremely potent whole-protein vaccine, eliciting endogenous T-cell and antibody responses comparable to the strongest vaccine vectors. These materials should enable a range of subunit vaccines and provide new possibilities for protein therapeutic delivery.
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Cites
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Nanotechnology for protein delivery: Overview and perspectives
Yu, M., Wu, J., Shi, J., & Farokhzad, O. C. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.10.012 · Cited by 410
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Metadata
- Authors
- Moon, J. J., Suh, H., Bershteyn, A., Stephan, M. T., Liu, H., Huang, B., Sohail, M., Luo, S., Ho Um, S., Khant, H., Goodwin, J. T., Ramos, J., Chiu, W., & Irvine, D. J.
- Venue
- Nature Materials
- Published
- 2011-02-20
- Volume
- 10
- Issue
- 3
- Pages
- 243-251
- ISSN
- 1476-1122 (ISSN-L)
- 1476-4660
- OpenAlex
- W1553974197
- Cited by
- 564
- References
- 4
- FWCI
- 14.24
- Type
- journal article
- Language
- en
- Open access
- green
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- Moon, J. J., Suh, H., Bershteyn, A., Stephan, M. T., Liu, H., Huang, B., Sohail, M., Luo, S., Ho Um, S., Khant, H., Goodwin, J. T., Ramos, J., Chiu, W., & Irvine, D. J. (2011). Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses. Nature Materials. https://doi.org/10.1038/nmat2960
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