An IL-12 mRNA-LNP adjuvant enhances mRNA-LNP vaccine induced CD8+ T cell responses

The design of vaccines that induce CD8+ T cell responses has historically been a challenge, but the development of viral vectors or lipid nanoparticles (LNPs) to deliver mRNA that encode for target antigens provide more effective strategies to generate protective CD8+ T cell memory. Because interleukin-12 (IL-12) supports CD8+ T cell expansion and acquisition of effector functions, studies were performed to assess its contribution to the ability of an mRNA-LNP vaccine to promote CD8+ T cell responses. In vitro and in vivo, mRNA-LNPs did not stimulate myeloid cell production of IL-12, and the CD8+ T cell response to vaccination with the model antigen ovalbumin (OVA) was IL-12 independent. However, co-administration of IL-12 mRNA-LNPs with OVA mRNA-LNPs enhanced OVA-specific CD8+ T cell expansion, improved acquisition of effector function and resulted in an expanded memory CD8+ T cell pool. These heightened responses were associated with improved protective responses against Listeria monocytogenes-OVA and B16 F0-OVA melanoma. Thus, modification of mRNA vaccine formulations by inclusion of a cytokine mRNA provides a strategy to enhance CD8+ T cell mediated protection.