Temporal release of a three-component protein subunit vaccine from polymer multilayers
| Autor: | Jianzhu Chen, Julien Lescar, Victor Ho, Divakara S. S. M. Uppu, Paula T. Hammond, Yanpu He, Michelle E. Turvey, Ern Yu Tan, Katell Bidet, Anagha D. Tambe, Abdul Rahim Mohammed Sharif, Katja Fink |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Polymers
medicine.medical_treatment Protein subunit Pharmaceutical Science 02 engineering and technology Mice 03 medical and health sciences Immune system Adjuvants Immunologic Antigen In vivo medicine Animals 030304 developmental biology 0303 health sciences Chemistry Immunogenicity Vaccination 021001 nanoscience & nanotechnology Cell biology Protein Subunits Vaccines Subunit 0210 nano-technology Adjuvant Ex vivo |
| Zdroj: | Journal of Controlled Release. 317:130-141 |
| ISSN: | 0168-3659 |
| Popis: | Sustained antigen and adjuvant availability have been shown to improve antiviral immune responses following vaccination. Transcutaneous delivery of vaccines using microneedles has also shown promise and may be particularly relevant for mosquito-borne viruses. We aim to combine these traits to create a three-component Protein Subunit vaccine on Microneedle Arrays (PSMNs) for transcutaneous delivery using layer-by-layer (LbL) assembly. Polymer multilayer thin films were generated to co-deliver a model combination of three chemically distinct vaccine components, a dengue virus Envelope protein Domain III (EDIII) subunit antigen and two adjuvants, a double-stranded RNA (Poly (inosinic:cytidylic acid) (PolyI:C)) and an amphiphilic hexapeptide, Pam3CSK4. Following application of PSMNs to the skin, implanted thin films facilitated sustained and temporal release of individual vaccine components from polymer multilayers. By modulating LbL composition and architecture, component release profiles in the skin could be independently tuned to allow release of adjuvants and antigen from days up to two weeks. Uptake of antigen and adjuvant from implanted vaccine films by antigen-presenting cells was demonstrated using in vivo mouse and ex vivo human skin models. Overall, we believe that such modular vaccine strategies offer design principles for enhancing the immunogenicity of protein subunit vaccines. |
| Databáze: | OpenAIRE |
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