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Type VI secretion system sheaths as nanoparticles for antigen display.

Elena Del Tordello1, Olga Danilchanka1, Andrew J McCluskey1

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Proceedings of the National Academy of Sciences of the United States of America
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Summary

Bacterial type 6 secretion system (T6SS) sheaths were engineered into nanoparticles for vaccine delivery. These T6SS nanoparticles elicited stronger immune responses than soluble antigens, showing potential for new vaccine development.

Keywords:
antigenimmunogennanoparticlestype 6 secretion systemvaccine delivery

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Area of Science:

  • Microbiology
  • Immunology
  • Biotechnology

Background:

  • The bacterial type 6 secretion system (T6SS) is a protein-channeling machine.
  • T6SS sheaths, built from VipA-VipB heterodimers, resemble phage tails and are stable structures.
  • Harnessing biological structures for medical applications is an active area of research.

Purpose of the Study:

  • To investigate the potential of T6SS sheaths as a scaffold for vaccine delivery.
  • To evaluate the immunogenicity of T6SS sheath-based nanoparticles displaying foreign antigens.

Main Methods:

  • Engineered VipA and VipB proteins fused to target antigens.
  • Purified T6SS sheaths from Vibrio cholerae or Escherichia coli expressing these fusion proteins.
  • Immunized mice with the T6SS sheath nanoparticles and assessed immune responses.

Main Results:

  • T6SS sheaths displaying heterologous antigens induced superior immune responses compared to soluble antigens.
  • The induced antibodies targeted specific IgG subclasses.
  • Antibodies generated against a Neisseria meningitidis antigen were functional in serum bactericidal assays.

Conclusions:

  • T6SS sheaths can be repurposed as multivalent nanoparticles for vaccine development.
  • This T6SS-based nanoparticle system offers a versatile platform for generating robust immune responses.