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Multi-Antigen Outer Membrane Vesicle Engineering to Develop Polyvalent Vaccines: The Staphylococcus aureus Case.

Enrico König1, Assunta Gagliardi2, Ilary Riedmiller1

  • 1Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.

Frontiers in Immunology
|November 25, 2021
PubMed
Summary

This study presents a novel strategy for developing multi-antigen vaccines using engineered bacterial outer membrane vesicles (OMVs). The developed tetravalent vaccine effectively protects against Staphylococcus aureus infections in preclinical models.

Keywords:
OMV engineeringStaphylococcus aureuschimeric proteinsmultivalent vaccinesouter membrane vesicles (OMVs)

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Area of Science:

  • Vaccinology
  • Microbial Pathogenesis
  • Biotechnology

Background:

  • Pathogens evade immune responses through surface antigen modification and virulence factor expression, complicating vaccine development.
  • Developing effective vaccines requires targeting multiple antigens, posing a challenge for traditional vaccine design.
  • Bacterial Outer Membrane Vesicles (OMVs) offer a versatile platform for vaccine development due to their adjuvant properties and engineering flexibility.

Purpose of the Study:

  • To establish and validate a generalized strategy for co-expressing multiple antigens within a single OMV vaccine.
  • To develop a multi-component OMV-based vaccine targeting key virulence factors of *Staphylococcus aureus*.
  • To assess the immunogenicity and protective efficacy of the developed tetravalent *S. aureus* OMV vaccine.

Main Methods:

  • Engineered an OMV-producing strain for co-expression of two chimeric proteins, each fusing multiple immunogenic antigens.
  • Constructed a tetravalent vaccine (CLSH-OMVsΔ60) by co-expressing modified *S. aureus* virulence factors: ClfAY338A, LukE, SpAKKAA, and HlaH35L.
  • Evaluated vaccine efficacy in mouse models of *S. aureus* skin infection, sepsis, and kidney abscesses.

Main Results:

  • The CLSH-OMVsΔ60 vaccine successfully elicited functional, antigen-specific antibodies.
  • Antibodies demonstrated opsonophagocytic activity and inhibited key virulence mechanisms: Hla-mediated hemolysis, LukED-mediated leukocyte killing, and ClfA-mediated bacterial binding.
  • Vaccinated mice showed robust protection against *S. aureus* challenge across multiple infection models.

Conclusions:

  • The co-expression strategy provides a generalized and simplified approach for creating multi-component vaccines.
  • The developed tetravalent *S. aureus* OMV vaccine (CLSH-OMVsΔ60) is a promising candidate for further development.
  • This platform enables the cost-effective production of advanced, multi-target vaccines against challenging pathogens.