An <i>Il12</i> mRNA-LNP adjuvant enhances mRNA vaccine–induced CD8 T cell responses
Emily Aunins, Anthony T. Phan, Mohamad‐Gabriel Alameh, Garima Dwivedi, Elisa Cruz-Morales, David A. Christian, Ying K. Tam, Molly Bunkofske, Anabel Zabala Peñafiel, Keenan M. O’Dea, Maria Merolle, Colleen Furey, Phillip Scott, Robert H. Vonderheide, Scott E. Hensley, Ross M. Kedl, Drew Weissman, Christopher A. Hunter
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.