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March 14, 2026Science Advances2 citationsOpen Access

Integrated reiterative pipeline for rapid epitope-based pan-alphavirus vaccines

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AVAlice F. VersianiPMPeter McCaffreyR1Ribeiro-Filho, Helder Veras, 1988-

Key Points

  • To establish a rapid and adaptable vaccine development pipeline targeting alphaviruses.
  • Integrated machine learning-based epitope prediction and protein modeling
  • Utilized peptide microarrays to validate T cell epitopes
  • Conducted molecular dynamics simulations for binding accuracy
  • Performed flow cytometry on murine and human samples
  • Selected candidates based on composite immunogenicity scores.
  • Confirmed T cell activation from selected viral peptides
  • Achieved robust cytokine secretion responses
  • Developed a multitarget vaccine design pipeline
  • Validated binding accuracy through molecular simulations
  • Highlighted ongoing efforts in B cell epitope analysis.

Abstract

The vast diversity of the virosphere underscores the need for rapid, adaptable vaccine development infrastructures. Arthropod-borne zoonotic alphaviruses, in particular, continue to pose substantial threats to human and animal health. We present a fast, multitarget vaccine design pipeline integrating machine learning-based epitope prediction, protein modeling, and docking to prioritize viral peptides by immunogenicity, allele coverage, solubility, and stability. T cell epitopes were validated using peptide microarrays and molecular dynamics simulations, confirming receptor binding accuracy. Flow cytometry of murine and human peripheral blood mononuclear cells demonstrated robust T cell activation and cytokine secretion (IFN-γ, TNF-α, or IL-2), dependent on species and HLA allele. Final candidates were selected by composite immunogenicity scores. While this study primarily validates the T cell-specific arm of our predictive pipeline, complementary B cell epitope analyses are ongoing. Our findings support the development of broadly protective pan-alphaviral vaccines and the establishment of efficient, tunable processes for global vaccine development.

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Cite This Study

Versiani et al. (2026) studied this question.

synapsesocial.com/papers/69b4ba0818185d8a39802738https://doi.org/10.1126/sciadv.aeb2066
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