An mRNA vaccine encoding proteasome-targeted antigen enhances CD8⁺ T cell immunity

Area of Science:

• Immunology
• Vaccinology
• Molecular Biology

Background:

• Efficient induction of antigen-specific CD8+ T cell activation is critical for mRNA tumor vaccine efficacy.
• The ubiquitin-proteasome system and MHC-I pathway are key for endogenous antigen presentation and T cell activation.

Purpose of the Study:

• To develop a novel mRNA vaccine by fusing an antigen with a proteasome-targeting peptide (PTP).
• To enhance proteasomal degradation of antigens and improve CD8+ T cell immune responses.

Main Methods:

• Constructed an mRNA vaccine encoding an antigen fused with a PTP.
• Administered the PTP-mRNA vaccine intramuscularly in TC-1 tumor-bearing mice.
• Assessed antigen expression, MHC-I pathway gene expression, immune cell activation, tumor growth, and immune memory.

Main Results:

• Increased antigen expression and MHC-I pathway gene upregulation were observed with the PTP-mRNA vaccine.
• Enhanced activation of dendritic cells, macrophages, and T cells in lymphoid organs.
• Significant tumor growth suppression, increased intratumoral CD8+ T cell infiltration, and robust immune memory induction.

Conclusions:

• The PTP-mRNA vaccine strategy effectively enhances antigen processing and presentation via the ubiquitin-proteasome and MHC-I pathways.
• This approach significantly boosts anti-tumor immunity, leading to suppressed tumor growth and established immune memory.