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<p>The mRNA-LNP-based SARS-CoV-2 vaccines were a breakthrough for the technology; however, their production requires specialized equipment, and the complex formulation involving four distinct lipid classes imposes stringent requirements on both characterization and quality control. We tested a cationic adjuvant formulation containing a simple two-component liposome formulation based on dimethyldioctadecylammonium bromide and monomycoloyl glycerol-1 (CAF<sup>®</sup>04) for mRNA-delivery, which can be complexed with mRNA by simple admixing on-site. The physicochemical characteristics of the resulting vaccine particles depended on the CAF04:mRNA N/P ratio, where an N/P ratio ≤ 1.09 resulted in anionic particles with little aggregation and N/P ratios ≥ 2.18 resulted in increasingly cationic particles that aggregated. These attributes influenced the magnitude of the CD8<sup>+</sup> T-cell responses induced against OVA-encoding mRNA and at optimal CAF04:mRNA N/P ratios (0.76–1.42), the antigen-specific CD8<sup>+</sup> T-cell responses reached magnitudes comparable to the DOTMA:DOPE Lipoplex (RNA-LPX) platform. Therapeutic vaccination using CAF04:mRNA delayed tumor growth and enhanced survival in an E.G7-OVA lymphoma model. We present a highly stable mRNA delivery platform that can be freeze-dried for extended storage and admixed with mRNA on-site to induce highly functional CD8<sup>+</sup> T-cell responses with potential for therapeutic cancer vaccines.</p> Graphical Abstract <p></p>

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A stable two-component cationic liposome platform for mRNA delivery induces CD8+ T-cell responses and protection in a murine lymphoma model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月7日

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  • Gabriel Kristian Pedersen,
  • Reham Sabah Alhakeem,
  • Ahmad Tami,
  • Dennis Christensen,
  • Zahra Shabanian,
  • Rune Fledelius Jensen,
  • Katharina Wørzner,
  • Signe Tandrup Schmidt

摘要

The mRNA-LNP-based SARS-CoV-2 vaccines were a breakthrough for the technology; however, their production requires specialized equipment, and the complex formulation involving four distinct lipid classes imposes stringent requirements on both characterization and quality control. We tested a cationic adjuvant formulation containing a simple two-component liposome formulation based on dimethyldioctadecylammonium bromide and monomycoloyl glycerol-1 (CAF®04) for mRNA-delivery, which can be complexed with mRNA by simple admixing on-site. The physicochemical characteristics of the resulting vaccine particles depended on the CAF04:mRNA N/P ratio, where an N/P ratio ≤ 1.09 resulted in anionic particles with little aggregation and N/P ratios ≥ 2.18 resulted in increasingly cationic particles that aggregated. These attributes influenced the magnitude of the CD8+ T-cell responses induced against OVA-encoding mRNA and at optimal CAF04:mRNA N/P ratios (0.76–1.42), the antigen-specific CD8+ T-cell responses reached magnitudes comparable to the DOTMA:DOPE Lipoplex (RNA-LPX) platform. Therapeutic vaccination using CAF04:mRNA delayed tumor growth and enhanced survival in an E.G7-OVA lymphoma model. We present a highly stable mRNA delivery platform that can be freeze-dried for extended storage and admixed with mRNA on-site to induce highly functional CD8+ T-cell responses with potential for therapeutic cancer vaccines.

Graphical Abstract