Efficient induction of antigen-specific CD8(+) T-cell responses by cationic peptide-based mRNA nanoparticles

Sigrid D'haese, Thessa Laeremans, Sabine den Roover, Sabine D. Allard, Guido Vanham, Joeri L. Aerts

Research output: Contribution to journalA1: Web of Science-articlepeer-review

7 Downloads (Pure)

Abstract

A major determinant for the success of mRNA-based vaccines is the composition of the nanoparticles (NPs) used for formulation and delivery. Cationic peptides represent interesting candidate carriers for mRNA, since they have been shown to efficiently deliver nucleic acids to eukaryotic cells. mRNA NPs based on arginine-rich peptides have previously been demonstrated to induce potent antigen-specific CD8(+) T-cell responses. We therefore compared the histidine-rich amphipathic peptide LAH4-L1 (KKALLAHALHLLALLALHLAHALKKA) to the fully substituted arginine variant (LAH4-L1R) for their capacity to formulate mRNA and transfect dendritic cells (DCs). Although both peptides encapsulated mRNA to the same extent, and showed excellent uptake in DCs, the gene expression level was significantly higher for LAH4-L1. The LAH4-L1-mRNA NPs also resulted in enhanced antigen presentation in the context of MHC I compared to LAH4-L1R in primary murine CD103(+) DCs. Both peptides induced DC maturation and inflammasome activation. Subsequent ex vivo stimulation of OT-I splenocytes with transfected CD103(+) DCs resulted in a high proportion of polyfunctional CD8(+) T cells for both peptides. In addition, in vivo immunization with LAH4-L1 or LAH4-L1R-mRNA NPs resulted in proliferation of antigen-specific T cells. In conclusion, although LAH4-L1 outperformed LAH4-L1R in terms of transfection efficiency, the immune stimulation ex vivo and in vivo was equally efficient.

Original languageEnglish
Article number1387
JournalPharmaceutics
Volume14
Issue number7
Number of pages19
DOIs
Publication statusPublished - 2022

Keywords

  • mRNA
  • nanoparticles
  • nanovaccines
  • HISTIDINE-RICH PEPTIDES
  • DENDRITIC CELLS
  • DELIVERY
  • INFLAMMASOMES
  • ACTIVATION
  • EXPANSION
  • ARGININE
  • VECTOR
  • LAH4

Fingerprint

Dive into the research topics of 'Efficient induction of antigen-specific CD8(+) T-cell responses by cationic peptide-based mRNA nanoparticles'. Together they form a unique fingerprint.

Cite this