Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses
| Autor: | Jenelyn Ramos, Matthias Stephan, Anna Bershteyn, Bonnie Huang, Soong Ho Um, Wah Chiu, Mashaal Sohail, James J. Moon, Jessica T. Goodwin, Darrell J. Irvine, Heikyung Suh, Htet A. Khant, Haipeng Liu, Samantha S. Luo |
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| Rok vydání: | 2011 |
| Předmět: |
Ovalbumin
medicine.medical_treatment Lipid Bilayers 02 engineering and technology Lymphocyte Activation Article Mice 03 medical and health sciences Immune system Adjuvants Immunologic Antigen medicine Animals General Materials Science Lipid bilayer 030304 developmental biology Drug Carriers Immunity Cellular Vaccines Synthetic 0303 health sciences Attenuated vaccine Chemistry Mechanical Engineering Immunogenicity Vesicle Viral Vaccine technology industry and agriculture Viral Vaccines General Chemistry 021001 nanoscience & nanotechnology Condensed Matter Physics Molecular biology Immunity Humoral 3. Good health Cell biology Mice Inbred C57BL Mechanics of Materials Drug Design Liposomes 0210 nano-technology Immunologic Memory Adjuvant |
| Zdroj: | Nature materials |
| ISSN: | 1476-4660 1476-1122 |
| DOI: | 10.1038/nmat2960 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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