Cells

Improved surrounding protein sequences boost immune response and antigen display after mRNA vaccination

Updated

Abstract

The vaccine encoding tumor-specific antigens with optimized flanking sequences cleared established tumors and elicited robust CD8+ T-cell responses.

  • Two mRNA vaccines were designed to encode the same tumor-specific antigens but differed in their epitope-flanking amino acids.
  • The vaccine with optimized flanking sequences (TSA-Opti) was associated with stronger immune responses compared to the one with natural flanking sequences (TSA-Nat).
  • Quantitative analysis indicated that TSA-Opti increased the levels of antigen presentation.
  • Enhanced antigen presentation correlated with greater magnitude, clonal diversity, and functionality of CD8+ T cells specific to the tumor antigens.
  • TSA-Opti also promoted durable immune memory, suggesting long-term protection against tumor re-exposure.

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