Oral vaccination against plague using Yersinia pseudotuberculosis

Area of Science:

• Microbiology
• Immunology
• Vaccinology

Background:

• Yersinia pestis causes plague, a deadly disease with re-emerging outbreaks and potential bioterrorism applications.
• Antibiotic resistance in Yersinia pestis necessitates alternative prevention strategies like vaccination.
• A globally licensed vaccine against plague is currently unavailable.

Purpose of the Study:

• To develop a safe and immunogenic oral vaccine against Yersinia pestis.
• To enhance cross-species immunogenicity for broader protection.
• To evaluate the efficacy of the vaccine against different Yersinia pestis strains.

Main Methods:

• Attenuated Yersinia pseudotuberculosis strain IP32953 was genetically modified by deleting genes for three essential virulence factors.
• The Yersinia pestis caf operon encoding the F1 antigen was inserted into the Yersinia pseudotuberculosis chromosome to create an F1-encapsulated strain.
• The final vaccine candidate, VTnF1, was tested for its protective efficacy against bubonic and pneumonic plague forms.

Main Results:

• The modified Yersinia pseudotuberculosis strain, VTnF1, demonstrated high efficacy and long-lasting protection against plague after a single oral dose.
• VTnF1 provided complete protection against both bubonic and pneumonic plague, even against Yersinia pestis strains lacking the F1 antigen.
• The vaccine induced a protective immune response, with modifications impacting bacterial virulence and immunogenicity.

Conclusions:

• VTnF1 is a highly efficient vaccine candidate for mass vaccination in plague-endemic areas and for bioterrorism preparedness.
• The oral administration route and single-dose regimen offer practical advantages for large-scale deployment.
• The vaccine's efficacy against F1-deficient strains broadens its potential applicability.