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Lipid-polyglutamate nanoparticle vaccine platform

Dorien Van Lysebetten, Alessio Malfanti, Kim Deswarte (UGent) , Kaloian Koynov, Bianka Golba (UGent) , Tingting Ye (UGent) , Zifu Zhong (UGent) , Sabah Kasmi (UGent) , Alexander Lamoot (UGent) , Yong Chen (UGent) , et al.
Author
Organization
Abstract
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.
Keywords
General Materials Science, vaccine, lipid nanoparticles, peptides, TLR agonists

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MLA
Van Lysebetten, Dorien, et al. “Lipid-Polyglutamate Nanoparticle Vaccine Platform.” ACS APPLIED MATERIALS & INTERFACES, vol. 13, no. 5, 2021, pp. 6011–22, doi:10.1021/acsami.0c20607.
APA
Van Lysebetten, D., Malfanti, A., Deswarte, K., Koynov, K., Golba, B., Ye, T., … De Geest, B. (2021). Lipid-polyglutamate nanoparticle vaccine platform. ACS APPLIED MATERIALS & INTERFACES, 13(5), 6011–6022. https://doi.org/10.1021/acsami.0c20607
Chicago author-date
Van Lysebetten, Dorien, Alessio Malfanti, Kim Deswarte, Kaloian Koynov, Bianka Golba, Tingting Ye, Zifu Zhong, et al. 2021. “Lipid-Polyglutamate Nanoparticle Vaccine Platform.” ACS APPLIED MATERIALS & INTERFACES 13 (5): 6011–22. https://doi.org/10.1021/acsami.0c20607.
Chicago author-date (all authors)
Van Lysebetten, Dorien, Alessio Malfanti, Kim Deswarte, Kaloian Koynov, Bianka Golba, Tingting Ye, Zifu Zhong, Sabah Kasmi, Alexander Lamoot, Yong Chen, Simon Van Herck, Bart Lambrecht, Niek Sanders, Stefan Lienenklaus, Sunil A. David, María J. Vicent, Stefaan De Koker, and Bruno De Geest. 2021. “Lipid-Polyglutamate Nanoparticle Vaccine Platform.” ACS APPLIED MATERIALS & INTERFACES 13 (5): 6011–6022. doi:10.1021/acsami.0c20607.
Vancouver
1.
Van Lysebetten D, Malfanti A, Deswarte K, Koynov K, Golba B, Ye T, et al. Lipid-polyglutamate nanoparticle vaccine platform. ACS APPLIED MATERIALS & INTERFACES. 2021;13(5):6011–22.
IEEE
[1]
D. Van Lysebetten et al., “Lipid-polyglutamate nanoparticle vaccine platform,” ACS APPLIED MATERIALS & INTERFACES, vol. 13, no. 5, pp. 6011–6022, 2021.
@article{8702822,
  abstract     = {{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.}},
  author       = {{Van Lysebetten, Dorien and Malfanti, Alessio and Deswarte, Kim and Koynov, Kaloian and Golba, Bianka and Ye, Tingting and Zhong, Zifu and Kasmi, Sabah and Lamoot, Alexander and Chen, Yong and Van Herck, Simon and Lambrecht, Bart and Sanders, Niek and Lienenklaus, Stefan and David, Sunil A. and Vicent, María J. and De Koker, Stefaan and De Geest, Bruno}},
  issn         = {{1944-8244}},
  journal      = {{ACS APPLIED MATERIALS & INTERFACES}},
  keywords     = {{General Materials Science,vaccine,lipid nanoparticles,peptides,TLR agonists}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{6011--6022}},
  title        = {{Lipid-polyglutamate nanoparticle vaccine platform}},
  url          = {{http://doi.org/10.1021/acsami.0c20607}},
  volume       = {{13}},
  year         = {{2021}},
}

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