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Related Experiment Video

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A synthetic delivery vector for mucosal vaccination.

Anne Billet1, Justine Hadjerci2, Thi Tran3

  • 1Institut Curie, Université PSL, Cellular and Chemical Biology Unit, U1143 INSERM, UMR3666 CNRS, 26 Rue d'Ulm, 75248, Paris, Cedex 05, France; Université de Paris, 85 boulevard Saint-Germain, 75006, Paris, France.

Biomaterials
|September 15, 2023
PubMed
Summary

Researchers developed a synthetic STxB protein for mucosal vaccines. This new delivery tool effectively induces immune responses against SARS-CoV-2 and HPV, addressing limitations of current mRNA vaccines.

Keywords:
Mucosal immunityResident memory T cellsShiga toxin B-SubunitSolid phase peptide synthesisVaccination

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Area of Science:

  • Vaccinology
  • Immunology
  • Protein Chemistry

Background:

  • mRNA vaccines showed success against COVID-19 but have limitations.
  • Current vaccines show modest CD8+ T cell responses and lack mucosal immunity.
  • Mucosal immunity is crucial for preventing viral spread in the general population.

Purpose of the Study:

  • To develop a novel dendritic cell-targeting mucosal vaccination vector.
  • To create a synthetic delivery tool for enhanced vaccine efficacy.
  • To generate STxB variants for antigen coupling and mucosal immunization.

Main Methods:

  • Efficient chemical synthesis and in vitro folding of homopentameric STxB protein.
  • Generation of STxB variants with bioorthogonal handles for antigen conjugation.
  • Intranasal administration of STxB-antigen conjugates in a mouse model.

Main Results:

  • Synthetic STxB exhibited comparable biophysical and intracellular trafficking to recombinant STxB.
  • Chemically coupled STxB variants successfully delivered SARS-CoV-2 and HPV antigens.
  • Intranasal vaccination induced robust mucosal immunity, including resident memory CD8+ T cells and IgA antibodies.

Conclusions:

  • A novel synthetic antigen delivery tool, STxB, was developed for mucosal vaccination.
  • This approach overcomes limitations of mRNA vaccines by inducing strong mucosal immunity.
  • The synthetic STxB vector holds significant potential for addressing urgent medical needs in infectious disease prevention.