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VelcroVax: a "Bolt-On" Vaccine Platform for Glycoprotein Display.

Natalie J Kingston1, Keith Grehan1, Joseph S Snowden1

  • 1Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.

Msphere
|January 31, 2023
PubMed
Summary

A novel "bolt-on" vaccine platform, VelcroVax, uses modified virus-like particles to capture viral antigens. This system generates enhanced immune responses and offers a foundation for rapid vaccine development against emerging pathogens.

Keywords:
HBcAgJunín virusVLPplatformvaccine

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Area of Science:

  • Vaccinology
  • Structural biology
  • Immunology

Background:

  • Developing diverse vaccine manufacturing approaches is crucial for global health security and emerging infectious diseases.
  • Virus-like particles (VLPs) are effective vaccine platforms, forming the basis of successful vaccines against hepatitis B virus (HBV) and human papillomavirus.
  • VLPs can be engineered to display foreign antigens, enabling novel vaccine design strategies.

Purpose of the Study:

  • To describe and characterize a universal "bolt-on" vaccine platform, termed VelcroVax, for rapid antigen presentation.
  • To demonstrate the feasibility of capturing a target antigen using a modified VLP system.
  • To evaluate the immunogenicity of the resulting vaccine complex.

Main Methods:

  • Utilized a modified hepatitis B core antigen (HBcAg) VLP displaying an Affimer molecule for binding to a SUMO tag.
  • Captured SUMO-tagged gp1 glycoprotein from Junín virus (JUNV) onto the engineered HBcAg VLPs.
  • Determined high-resolution structures of the VelcroVax VLPs and the antigen complex.
  • Assessed humoral immune responses induced by the VelcroVax-JUNV gp1 complex.

Main Results:

  • Successfully engineered HBcAg VLPs to capture SUMO-tagged JUNV gp1.
  • Obtained the first high-resolution structural data for the VelcroVax system and its antigen complex.
  • The VelcroVax-JUNV gp1 complex elicited superior humoral immune responses compared to the non-complexed viral protein.

Conclusions:

  • The VelcroVax platform provides a versatile and adaptable system for nanoparticle vaccine development.
  • This platform facilitates the rapid generation of vaccine candidates by "bolting-on" various antigens.
  • VelcroVax holds significant potential for future rapid-response vaccination strategies against diverse pathogens.