tetano
Editor, Senior Moderator
Sci Immunol
. 2025 Jun 6;10(108):eads1328.
doi: 10.1126/sciimmunol.ads1328. Epub 2025 Jun 6. An Il12 mRNA-LNP adjuvant enhances mRNA vaccine-induced CD8 T cell responses
Emily A Aunins[SUP] 1 [/SUP], Anthony T Phan[SUP] 1 [/SUP], Mohamad-Gabriel Alameh[SUP] 2 3 4 [/SUP], Garima Dwivedi[SUP] 5 [/SUP], Elisa Cruz-Morales[SUP] 1 [/SUP], David A Christian[SUP] 1 [/SUP], Ying Tam[SUP] 6 [/SUP], Molly E Bunkofske[SUP] 1 [/SUP], Anabel Zabala Peñafiel[SUP] 1 [/SUP], Keenan M O'Dea[SUP] 1 [/SUP], Maria Merolle[SUP] 1 [/SUP], Colleen Furey[SUP] 7 [/SUP], Phillip Scott[SUP] 1 [/SUP], Robert H Vonderheide[SUP] 8 [/SUP], Scott E Hensley[SUP] 7 [/SUP], Ross M Kedl[SUP] 9 [/SUP], Drew Weissman[SUP] 4 5 [/SUP], Christopher A Hunter[SUP] 1 [/SUP]
Affiliations
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.
. 2025 Jun 6;10(108):eads1328.
doi: 10.1126/sciimmunol.ads1328. Epub 2025 Jun 6. An Il12 mRNA-LNP adjuvant enhances mRNA vaccine-induced CD8 T cell responses
Emily A Aunins[SUP] 1 [/SUP], Anthony T Phan[SUP] 1 [/SUP], Mohamad-Gabriel Alameh[SUP] 2 3 4 [/SUP], Garima Dwivedi[SUP] 5 [/SUP], Elisa Cruz-Morales[SUP] 1 [/SUP], David A Christian[SUP] 1 [/SUP], Ying Tam[SUP] 6 [/SUP], Molly E Bunkofske[SUP] 1 [/SUP], Anabel Zabala Peñafiel[SUP] 1 [/SUP], Keenan M O'Dea[SUP] 1 [/SUP], Maria Merolle[SUP] 1 [/SUP], Colleen Furey[SUP] 7 [/SUP], Phillip Scott[SUP] 1 [/SUP], Robert H Vonderheide[SUP] 8 [/SUP], Scott E Hensley[SUP] 7 [/SUP], Ross M Kedl[SUP] 9 [/SUP], Drew Weissman[SUP] 4 5 [/SUP], Christopher A Hunter[SUP] 1 [/SUP]
Affiliations
- PMID: 40478935
- DOI: 10.1126/sciimmunol.ads1328
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.