An <i>Il12</i> mRNA-LNP adjuvant enhances mRNA vaccine–induced CD8 T cell responses
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 <i>Listeria monocytogenes</i>-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.
Authors
- Christopher A. Hunter (ORCID: https://orcid.org/0000-0003-3092-1428)
- Molly Bunkofske (ORCID: https://orcid.org/0000-0003-1457-5641)
- Elisa Cruz-Morales (ORCID: https://orcid.org/0000-0003-4902-4372)
- Emily Aunins (ORCID: https://orcid.org/0000-0003-2401-8224)
- Scott E. Hensley (ORCID: https://orcid.org/0000-0002-2928-7506)
- Robert H. Vonderheide (ORCID: https://orcid.org/0000-0002-7252-954X)
- Keenan M. O’Dea (ORCID: https://orcid.org/0000-0001-9278-0697)
- Garima Dwivedi (ORCID: https://orcid.org/0000-0002-6101-2481)
- Colleen Furey (ORCID: https://orcid.org/0000-0002-2846-5219)
- David A. Christian (ORCID: https://orcid.org/0000-0002-7160-9900)
- Phillip Scott (ORCID: https://orcid.org/0000-0001-8732-0653)
- Ying K. Tam (ORCID: https://orcid.org/0000-0002-4083-5251)
- Ross M. Kedl (ORCID: https://orcid.org/0000-0002-9065-7895)
- Drew Weissman (ORCID: https://orcid.org/0000-0002-1501-6510)
- Mohamad‐Gabriel Alameh (ORCID: https://orcid.org/0000-0002-5672-6930)
- Anthony T. Phan (ORCID: https://orcid.org/0000-0003-2935-6070)
- Maria Merolle (ORCID: https://orcid.org/0000-0002-5866-1835)
- Anabel Zabala Peñafiel
Institutions
- Children's Hospital of Philadelphia (US)
- Penn Center for AIDS Research (US)
- Acuitas Therapeutics (Canada) (CA)
- University of Colorado Anschutz Medical Campus (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Science Immunology
- Published
- 2025-06-06
- DOI
- https://doi.org/10.1126/sciimmunol.ads1328
- Citations
- 26
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 20.73