An Il12 mRNA-LNP adjuvant enhances mRNA vaccine-induced CD8 T cell responses

Sci Immunol. 2025 Jun 6;10(108):eads1328. doi: 10.1126/sciimmunol.ads1328. Epub 2025 Jun 6.

Abstract

Optimizing vaccine design to induce CD8 T cell responses has been challenging, but lipid nanoparticle (LNP)-encapsulated mRNA vaccines effectively generate CD8 T cell memory. Interleukin-12 (IL-12) supports CD8 T cell expansion and acquisition of effector function, but the role of IL-12 in the generation of CD8 T responses to mRNA vaccination is unclear. Here, we determine that endogenous IL-12 is not required for CD8 T cell responses to mRNA-LNP vaccination. We assessed the adjuvant activity of an mRNA-LNP encapsulating a codon-optimized mRNA that encodes both subunits of IL-12 (LNP-IL-12). Coadministration of LNP-IL-12 with ovalbumin (OVA) mRNA-LNPs enhanced CD8 T cell expansion and effector function and expanded circulating, effector, and tissue-resident memory CD8 T cells. LNP-IL-12 increased CD8 T cell responses against SARS-CoV-2 and influenza virus antigens and improved protection against Listeria monocytogenes-OVA and B16F0-OVA melanoma. Thus, modification of mRNA-LNP formulations to include a cytokine mRNA provides a strategy to enhance CD8 T cell-mediated protection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic* / administration & dosage
  • Animals
  • CD8-Positive T-Lymphocytes* / immunology
  • COVID-19 / immunology
  • COVID-19 / prevention & control
  • COVID-19 Vaccines* / immunology
  • Female
  • Immunologic Memory
  • Influenza Vaccines / immunology
  • Interleukin-12* / genetics
  • Interleukin-12* / immunology
  • Lipids* / immunology
  • Liposomes
  • Listeria monocytogenes / immunology
  • Listeriosis / immunology
  • Listeriosis / prevention & control
  • Melanoma, Experimental / immunology
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles* / administration & dosage
  • Nanoparticles* / chemistry
  • Ovalbumin / immunology
  • RNA, Messenger* / immunology
  • SARS-CoV-2 / immunology
  • mRNA Vaccines* / immunology

Substances

  • Interleukin-12
  • Adjuvants, Immunologic
  • mRNA Vaccines
  • RNA, Messenger
  • Lipid Nanoparticles
  • Ovalbumin
  • COVID-19 Vaccines
  • Lipids
  • Influenza Vaccines
  • Liposomes