Lipid-Polyglutamate Nanoparticle Vaccine Platform
| Autor: | Alexander Lamoot, Dorien Van Lysebetten, Kaloian Koynov, Alessio Malfanti, Stefaan De Koker, Bart N. Lambrecht, Kim Deswarte, María J. Vicent, Stefan Lienenklaus, Bianka Golba, Tingting Ye, Niek N. Sanders, Simon Van Herck, Bruno G. De Geest, Sabah Kasmi, Sunil A. David, Zifu Zhong, Yong Chen |
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| Rok vydání: | 2021 |
| Předmět: |
Materials science
Surface Properties medicine.medical_treatment Antigen presentation 02 engineering and technology lipid nanoparticles 010402 general chemistry 01 natural sciences Article TLR agonists Cell Line Mice chemistry.chemical_compound Immune system Adjuvants Immunologic Antigen vaccine medicine Animals General Materials Science Lymphocytes Particle Size Peptide sequence Mice Inbred BALB C Vaccines Innate immune system Molecular Structure Polyglutamate 021001 nanoscience & nanotechnology Lipids 3. Good health 0104 chemical sciences Cell biology Imidazoquinoline RAW 264.7 Cells Polyglutamic Acid chemistry peptides Nanoparticles 0210 nano-technology Adjuvant |
| Zdroj: | ACS Applied Materials & Interfaces r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) Centro de Investigación Principe Felipe (CIPF) ACS Appl Mater Interfaces r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) instname |
| ISSN: | 1944-8244 |
| Popis: | Peptide-based subunit vaccines are attractive in view of personalized cancer vaccination with neo-antigens, as well as for the design of the newest generation of vaccines against infectious diseases. Key to mounting robust antigen-specific immunity is delivery of antigen to antigen-presenting (innate immune) cells in lymphoid tissue with concomitant innate immune activation to promote antigen presentation to T cells and to shape the amplitude and nature of the immune response. Nanoparticles that co-deliver both peptide antigen and molecular adjuvants are well suited for this task. However, in the context of peptide-based antigen, an unmet need exists for a generic strategy that allows for co-encapsulation of peptide and molecular adjuvants due to the stark variation in physicochemical properties based on the amino acid sequence of the peptide. These properties also strongly differ from those of many molecular adjuvants. Here, we devise a lipid nanoparticle (LNP) platform that addresses these issues. Key in our concept is poly(L-glutamic acid) (PGA), which serves as a hydrophilic backbone for conjugation of, respectively, peptide antigen (Ag) and an imidazoquinoline (IMDQ) TLR7/8 agonist as a molecular adjuvant. Making use of the PGA's polyanionic nature, we condensate PGA-Ag and PGA-IMDQ into LNP by electrostatic interaction with an ionizable lipid. We show in vitro and in vivo in mouse models that LNP encapsulation favors uptake by innate immune cells in lymphoid tissue and promotes the induction of Ag-specific T cells responses both after subcutaneous and intravenous administration. |
| Databáze: | OpenAIRE |
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