Mutated and bacteriophage T4 nanoparticle arrayed F1-V immunogens from Yersinia pestis as next generation plague...

Area of Science:

• Microbiology
• Immunology
• Vaccine Development

Background:

• Pneumonic plague, caused by Yersinia pestis, is a deadly disease with no current FDA-approved vaccine.
• The F1 protein, a component of plague vaccines, tends to aggregate, hindering purification and efficacy.
• Yersinia pestis poses a significant bioterrorism threat.

Purpose of the Study:

• To design and construct novel plague vaccines offering complete protection against pneumonic plague.
• To overcome the aggregation issues of the F1 protein for improved vaccine development.
• To evaluate the immunogenicity and protective efficacy of new vaccine platforms.

Main Methods:

• Structure-based immunogen design to modify the F1 protein, preventing polymerization while retaining T cell epitopes.
• Fusion of the mutated F1 protein (F1mut-V) with the V antigen, a type three secretion system (T3SS) component.
• Arraying the F1mut-V protein onto phage T4 nanoparticles via the small outer capsid protein (Soc).
• Testing soluble F1mut-V and T4-decorated F1mut-V vaccines in mouse and rat models against Yersinia pestis challenge.

Main Results:

• The mutated F1 protein (F1mut-V) exhibited significantly improved solubility as a monomer.
• T4-decorated F1mut-V induced balanced TH1 and TH2 immune responses in mice without adjuvant.
• Both soluble and T4-decorated F1mut-V vaccines conferred 100% protection against high-dose pneumonic plague challenge in mice and rats.
• Inclusion of YscF slightly enhanced vaccine potency, while V antigen modification did not improve efficacy.

Conclusions:

• Novel plague vaccine platforms utilizing structure-based design and T4 nanoparticle delivery are highly effective.
• These platforms overcome F1 protein aggregation issues, leading to soluble and immunogenic vaccine candidates.
• The developed vaccines provide complete protection against pneumonic plague, offering potential for next-generation plague vaccines.