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

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B948
Abstract ID: 6171

Presenting Author:
Emily A Aunins , Graduate Student at Univ. of Pennsylvania Sch. of Vet. Med.

Abstract:

The design of vaccines that can reliably induce protective CD8⁺ T cell activity has been considered a challenge for the vaccine field, but the use of viral vectors or mRNA encapsulated into lipid nanoparticles (LNPs) has overcome some of these issues. Because the cytokine 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 mRNA vaccines to promote CD8⁺ T cell responses.  mRNA-LNPs do not stimulate macrophage production of IL-12 in vitro nor does in vivo vaccination, and endogenous IL-12 is not required for the CD8⁺ T cell response to mRNA vaccination. However, the addition of IL-12 mRNA-LNPs into vaccination with LNPs that contain mRNA for the model antigen ovalbumin (OVA) results in enhanced OVA-specific CD8⁺ T cell expansion, improved acquisition of effector function, diversification of the CD8⁺ T cell effector pool through generation of a KLRG1^hi effector subset and expanded effector and central memory CD8⁺ T cell populations. In both preventative vaccination against Listeria monocytogenes-OVA and therapeutic vaccination against B16 F0-OVA melanoma, addition of IL-12 mRNA-LNPs enhanced protection. Thus, modification of current mRNA vaccine formulations to induce IL-12 production provides a strategy to modify the CD8⁺ T cell response, enhance CD8⁺ T cell mediated protection and illustrates the utility of cytokine mRNA to tailor vaccine-induced immunity.