IL-12 mRNA-LNP Adjuvant Enhances Immune Efficacy

In today's global public health field, vaccination is undoubtedly the key line of defense against infectious diseases. From the raging of the COVID-19 pandemic to the normalized prevention and control of various infectious diseases, the importance of vaccines is self-evident. However, how to improve the immune efficacy of vaccines, especially to enhance CD8 T cell-mediated immune responses, has always been a hot topic for scientists.

Recently, in a research report entitled "An Il12 mRNA-LNP adjuvant enhances mRNA vaccine–induced CD8 T cell responses" published in the international journal Science Immunology, scientists from the University of Pennsylvania and other institutions explored the potential of IL-12 mRNA-LNP as a new adjuvant in enhancing the CD8 T cell response induced by mRNA vaccines. This discovery not only provides new ideas for vaccine development, but also brings new hope for the future fight against infectious diseases and cancer.

Due to the advantages of rapid development and production, mRNA vaccines have shined in responding to sudden infectious diseases, but there is still room for improvement in inducing CD8 T cell immune responses. Developing strategies to enhance the CD8 T cell response induced by mRNA vaccines is extremely critical to improving the protective effect of vaccines. IL-12 is an important cytokine that promotes the expansion and function of CD8 T cells. Therefore, in this study, the researchers aimed to explore whether IL-12 mRNA-LNP, as an adjuvant, can enhance the CD8 T cell response induced by mRNA vaccines and evaluate its potential in long-term immune protection.

The experimental subjects of this study were C57BL/6 mice, which were used to evaluate the immune effect of the vaccine. The researchers used a variety of materials, including mRNA-LNP encoding ovalbumin (OVA) (LNP-OVA) and mRNA-LNP encoding IL-12 (LNP-IL-12). IL-12 is an important cytokine that promotes the expansion and effector function of CD8 T cells. In addition, they also used a variety of flow cytometry antibodies to detect the phenotype and function of CD8 T cells.

Figure 1. Incorporation of LNP-IL-12 enhances vaccine-specific CD8 T cell expansion and alters effector differentiation. (Aunins, Emily A., et al. 2025)

The experimental process mainly includes the following steps:

1. Vaccine preparation: The researchers prepared mRNA-LNP encoding OVA (LNP-OVA) and mRNA-LNP encoding IL-12 (LNP-IL-12). These mRNA-LNPs are encapsulated by lipid nanoparticles (LNPs) and can effectively deliver mRNA into cells.

2. Mouse immunization: After LNP-OVA and LNP-IL-12 were mixed, mice were immunized by intramuscular injection. In some experiments, control groups were set up for LNP-OVA or LNP-IL-12 alone.

3. Evaluation of immune effect: At different time points after immunization, the expansion, phenotype and function of CD8 T cells were detected by flow cytometry. In addition, the researchers also evaluated the protective effect of mice against Listeria monocytogenes and influenza virus.

The results showed that LNP-IL-12 can significantly enhance the CD8 T cell response induced by mRNA vaccines. Specifically, when LNP-OVA was used in combination with LNP-IL-12, the expansion of CD8 T cells increased more than fourfold compared to LNP-OVA alone, and these cells showed stronger effector functions, such as higher levels of IFN-γ and TNF-α secretion.

In addition, LNP-IL-12 also promoted the retention of CD8 T cells in tissues, forming a more powerful pool of tissue-resident memory CD8 T cells. In terms of protective effect, mice immunized with LNP-OVA and LNP-IL-12 showed significant protective effects when challenged with Listeria and influenza virus, and this protective effect lasted for several months.

This study has opened up new ideas for the development of mRNA vaccines. Encapsulating IL-12 mRNA in LNP can not only improve the immune efficacy of vaccines, but also reduce vaccine doses and side effects. LNP-IL-12 has good effects in multiple vaccine models and has broad application prospects. In the future, researchers will explore the safety and efficacy of IL-12 mRNA-LNP in other vaccine platforms and human clinical trials.