Acta biochimica et biophysica SinicaAug 4, 2026

Using a signal to direct proteins inside cells boosts antigen production and release to improve mRNA vaccine effectiveness

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 5, 2026

Abstract

Signal peptides from C3, IL-12, and IL-20 significantly enhance antigen expression and secretion levels in mRNA vaccines.

Signal peptides may improve the efficacy of mRNA vaccines by enhancing protein expression and immunogenicity.
The SARS-CoV-2 receptor-binding domain (RBD) serves as a model antigen for evaluating signal peptide effectiveness.
Fluorescence confocal microscopy shows improved targeting of mRNA to the endoplasmic reticulum with these signal peptides.
In vivo experiments indicate that mRNA vaccines with engineered signal peptides could induce stronger immune responses.

Simplified

The expression and secretion levels of antigenic proteins are critical determinants of mRNA vaccine efficacy. Signal peptides, which direct protein translocation into the endoplasmic reticulum (ER), have the potential to significantly enhance protein expression and immunogenicity, highlighting their value as engineering tools for mRNA vaccine design. This study adopts the SARS-CoV-2 RBD as a model antigen to screen a panel of signal peptides derived from common secretory proteins. The signal peptides from C3, IL-12, and IL-20 are identified as candidates capable of significantly promoting antigen expression and secretion. Fluorescence confocal microscopy reveals that these signal peptides enhance the targeting of mRNA to the ER at the subcellular level. In vivo experiments demonstrate that mRNA vaccines incorporating these engineered signal peptides induce stronger humoral and cellular immune responses. This study confirms that signal peptide replacement can enhance antigen expression, offering a potential strategy for improving the efficacy of mRNA vaccines.

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Using a signal to direct proteins inside cells boosts antigen production and release to improve mRNA vaccine effectiveness

Abstract

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