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March 25, 2026VaccinesOpen Access

Structural Design of T-Cell Epitope-Based mRNA Vaccine Constructs Determines the Quality of T-Cell Immunity and Protective Efficacy Against SARS-CoV-2 in Mice

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Authors

VGVladimir A. GushchinSechenov UniversityASAndrei E. SiniavinAPAndrei A. Pochtovyi

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Implication

Demonstrates how the structural design of mRNA vaccine constructs affects T-cell immunity in mice, suggesting better vaccine strategies.

Key Points

  • The aim is to understand how the design of mRNA vaccine constructs influences the quality of T-cell responses against SARS-CoV-2.
  • Designed ten tandem minigene mRNA constructs encoding SARS-CoV-2 epitopes.
  • Encapsulated constructs in lipid nanoparticles for delivery to C57BL/6 mice.
  • Assessed immunogenicity through cytokine profiling and T-cell proliferation assays.
  • Evaluated protective efficacy in K18-hACE2 transgenic mice challenged with SARS-CoV-2.
  • Constructs without signal peptides and rich in MHC class I epitopes showed strong CD8+ T-cell proliferation.
  • 66% survival rate after lethal challenge in mice with specific constructs.
  • Higher levels of IL-10 and IL-4 were linked to lower protective efficacy (11-33%).

Cite This Study

Gushchin et al. (2026) studied this question.

synapsesocial.com/papers/69c37ba2b34aaaeb1a67e406https://doi.org/10.3390/vaccines14030281
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