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Lipid nanoparticle encapsulation empowers poly(I:C) to activate cytoplasmic RLRs and thereby increases its adjuvanticity

Alexander Lamoot, Sonia Jangra, Gabriel Laghlali, Prajakta Warang, Gagandeep Singh, Lauren A. Chang, Seok‐Chan Park, Gagandeep Singh, Kim Deswarte (UGent) , Zifu Zhong (UGent) , et al.
(2024) SMALL. 20(10).
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Abstract
Poly(I:C) is a synthetic analogue of dsRNA capable of activating both TLR3 and RLRs, such as MDA-5 and RIG-I, as pathogen recognition receptors. While poly(I:C) is known to provoke a robust type I IFN, type III IFN, and Th1 cytokine response, its therapeutic use as a vaccine adjuvant is limited due to its vulnerability to nucleases and poor uptake by immune cells. is encapsulated poly(I:C) into lipid nanoparticles (LNPs) containing an ionizable cationic lipid that can electrostatically interact with poly(I:C). LNP-formulated poly(I:C) triggered both lysosomal TLR3 and cytoplasmic RLRs, in vitro and in vivo, whereas poly(I:C) in an unformulated soluble form only triggered endosomal-localized TLR3. Administration of LNP-formulated poly(I:C) in mouse models led to efficient translocation to lymphoid tissue and concurrent innate immune activation following intramuscular (IM) administration, resulting in a significant increase in innate immune activation compared to unformulated soluble poly(I:C). When used as an adjuvant for recombinant full-length SARS-CoV-2 spike protein, LNP-formulated poly(I:C) elicited potent anti-spike antibody titers, surpassing those of unformulated soluble poly(I:C) by orders of magnitude and offered complete protection against a SARS-CoV-2 viral challenge in vivo, and serum from these mice are capable of significantly reducing viral infection in vitro.
Keywords
Biomaterials, Biotechnology, General Materials Science, General Chemistry, immunotherapy, innate immune receptors, lipid nanoparticles, vaccine adjuvants, DENDRITIC CELLS, DUAL-DELIVERY, MESSENGER-RNA, RIG-I, RECOGNITION, RESPONSES, HYDROGEL, ANTIGENS, VACCINES, ROLES

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Citation

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MLA
Lamoot, Alexander, et al. “Lipid Nanoparticle Encapsulation Empowers Poly(I:C) to Activate Cytoplasmic RLRs and Thereby Increases Its Adjuvanticity.” SMALL, vol. 20, no. 10, 2024, doi:10.1002/smll.202306892.
APA
Lamoot, A., Jangra, S., Laghlali, G., Warang, P., Singh, G., Chang, L. A., … De Geest, B. (2024). Lipid nanoparticle encapsulation empowers poly(I:C) to activate cytoplasmic RLRs and thereby increases its adjuvanticity. SMALL, 20(10). https://doi.org/10.1002/smll.202306892
Chicago author-date
Lamoot, Alexander, Sonia Jangra, Gabriel Laghlali, Prajakta Warang, Gagandeep Singh, Lauren A. Chang, Seok‐Chan Park, et al. 2024. “Lipid Nanoparticle Encapsulation Empowers Poly(I:C) to Activate Cytoplasmic RLRs and Thereby Increases Its Adjuvanticity.” SMALL 20 (10). https://doi.org/10.1002/smll.202306892.
Chicago author-date (all authors)
Lamoot, Alexander, Sonia Jangra, Gabriel Laghlali, Prajakta Warang, Gagandeep Singh, Lauren A. Chang, Seok‐Chan Park, Gagandeep Singh, Kim Deswarte, Zifu Zhong, Benoit Louage, Emily De Lombaerde, Tingting Ye, Yong Chen, Sara Cuadrado‐Castano, Stefan Lienenklaus, Niek Sanders, Bart Lambrecht, Adolfo García‐Sastre, Michael Schotsaert, and Bruno De Geest. 2024. “Lipid Nanoparticle Encapsulation Empowers Poly(I:C) to Activate Cytoplasmic RLRs and Thereby Increases Its Adjuvanticity.” SMALL 20 (10). doi:10.1002/smll.202306892.
Vancouver
1.
Lamoot A, Jangra S, Laghlali G, Warang P, Singh G, Chang LA, et al. Lipid nanoparticle encapsulation empowers poly(I:C) to activate cytoplasmic RLRs and thereby increases its adjuvanticity. SMALL. 2024;20(10).
IEEE
[1]
A. Lamoot et al., “Lipid nanoparticle encapsulation empowers poly(I:C) to activate cytoplasmic RLRs and thereby increases its adjuvanticity,” SMALL, vol. 20, no. 10, 2024.
@article{01HH4GNT17GB33QBA5SYDGN8SN,
  abstract     = {{Poly(I:C) is a synthetic analogue of dsRNA capable of activating both TLR3 and RLRs, such as MDA-5 and RIG-I, as pathogen recognition receptors. While poly(I:C) is known to provoke a robust type I IFN, type III IFN, and Th1 cytokine response, its therapeutic use as a vaccine adjuvant is limited due to its vulnerability to nucleases and poor uptake by immune cells. is encapsulated poly(I:C) into lipid nanoparticles (LNPs) containing an ionizable cationic lipid that can electrostatically interact with poly(I:C). LNP-formulated poly(I:C) triggered both lysosomal TLR3 and cytoplasmic RLRs, in vitro and in vivo, whereas poly(I:C) in an unformulated soluble form only triggered endosomal-localized TLR3. Administration of LNP-formulated poly(I:C) in mouse models led to efficient translocation to lymphoid tissue and concurrent innate immune activation following intramuscular (IM) administration, resulting in a significant increase in innate immune activation compared to unformulated soluble poly(I:C). When used as an adjuvant for recombinant full-length SARS-CoV-2 spike protein, LNP-formulated poly(I:C) elicited potent anti-spike antibody titers, surpassing those of unformulated soluble poly(I:C) by orders of magnitude and offered complete protection against a SARS-CoV-2 viral challenge in vivo, and serum from these mice are capable of significantly reducing viral infection in vitro.}},
  articleno    = {{2306892}},
  author       = {{Lamoot, Alexander and Jangra, Sonia and Laghlali, Gabriel and Warang, Prajakta and Singh, Gagandeep and Chang, Lauren A. and Park, Seok‐Chan and Singh, Gagandeep and Deswarte, Kim and Zhong, Zifu and Louage, Benoit and De Lombaerde, Emily and Ye, Tingting and Chen, Yong and Cuadrado‐Castano, Sara and Lienenklaus, Stefan and Sanders, Niek and Lambrecht, Bart and García‐Sastre, Adolfo and Schotsaert, Michael and De Geest, Bruno}},
  issn         = {{1613-6810}},
  journal      = {{SMALL}},
  keywords     = {{Biomaterials,Biotechnology,General Materials Science,General Chemistry,immunotherapy,innate immune receptors,lipid nanoparticles,vaccine adjuvants,DENDRITIC CELLS,DUAL-DELIVERY,MESSENGER-RNA,RIG-I,RECOGNITION,RESPONSES,HYDROGEL,ANTIGENS,VACCINES,ROLES}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{14}},
  title        = {{Lipid nanoparticle encapsulation empowers poly(I:C) to activate cytoplasmic RLRs and thereby increases its adjuvanticity}},
  url          = {{http://doi.org/10.1002/smll.202306892}},
  volume       = {{20}},
  year         = {{2024}},
}
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