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Immune Modulator Encoded Lipid Nanoparticle Formulation Improves T Cell Response to Vaccines

Researchers developed an LNP-mRNA-based vaccine that encodes different cytokine mRNAs, as a method to enhance CD8+ T cell responses and memory formation.

Problem:

Lipid nanoparticles (LNPs) are an emerging technique to deliver mRNA in vivo more efficiently. While recent progress in mRNA technology has allowed the rapid development of SARS-COV2 vaccines, these protective responses often require high doses and boosting to generate long lived protective T cell responses.

Solution:

Dr. Hunter and his team have developed a method to promote T-cell immune responses to vaccines, by delivering mRNA that encodes cytokine (IL-12 or IL-27) concurrently with the antigen encoding mRNA. With this approach, they enable the future development of new vaccines by “mixing and matching” target antigens with different cytokines to enhance the memory T cell pool.

Technology:

The inventors previously discovered the importance of IL-27 in eliciting immune responses of CD8+ T cells post-mRNA LNP immunization. To validate this vaccine approach, the inventors first test IL-27 overexpression in vivo with a low dose of the antigen encoding mRNA. They then test the effects of the cytokine/antigen combination vaccine for restoring T cell expansion in IL-27 knock-out mice demonstrating the ability to produce functional cytokine in vivo. In wildtype mice administration of the cytokine/antigen combination vaccine improves the size of the CD8+ T cell memory pool, which is essential for long-term protection. Further, inclusion of cytokine mRNA improved the therapeutic efficacy of an anti-tumor antigen vaccine. Similar studies utilizing IL-12 mRNA showed that IL-12 could also be leveraged to improve memory CD8+ T cell formation and therapeutic efficacy of mRNA-LNPs to malignancy.

Advantages:

All the components of the LNP-mRNA vaccine can be modified, including the components that make up the LNPs and cytokine sequence
A small single dosage of the vaccine can induce a 10-fold increase in IL-12 or IL-27 expression in vivo
Cytokine mRNA (IL-12 or IL-27) improves the induction of antigen-specific CD8+ T cell responses to the vaccine
Cytokine mRNA (IL-12 or IL-27) augments memory CD8+ T cell pool
Cytokine mRNA (IL-12 or IL-27) enhances the efficacy of a therapeutic vaccine against murine melanoma