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Yersinia pestis YadC: a novel vaccine candidate against plague

Brian S Murphy1, Christine R Wulff, Beth A Garvy

  • 1Department of Internal Medicine, University of Kentucky, Lexington, USA. bsmurp1@uky.edu

Advances in Experimental Medicine and Biology
|October 31, 2007
PubMed

Insights

A new outer membrane protein, YadC, offers partial protection against F1(-) plague strains. Immunization with YadC in mice showed significant survival rates against pneumonic plague, suggesting a novel vaccine target.

Area of Science:

  • Microbiology
  • Immunology
  • Vaccinology

Background:

  • Current plague subunit vaccines offer limited protection against encapsulated (F1+) Yersinia pestis strains.
  • There is a need for vaccines effective against non-encapsulated (F1-) Y. pestis strains, which cause pneumonic plague.

Purpose of the Study:

  • To investigate the protective efficacy of YadC, a novel Y. pestis outer membrane protein, against F1(-) Y. pestis infection.
  • To compare the immune response elicited by YadC with that of LcrV, a component of current plague vaccines.

Main Methods:

  • Mice were immunized with purified fusion proteins (GST-YadC or HT-LcrV) with Alhydrogel adjuvant.
  • Mice were challenged intravenously or intranasally with virulent F1(-) Y. pestis strains.
  • Survival rates, antibody responses (IgG subclasses), and cytokine production from stimulated macrophages were analyzed.

Main Results:

  • Immunization with GST-YadC137-409 provided partial protection against pneumonic plague, with 87% survival in one model.
  • HT-LcrV immunization conferred full protection in one model and 50% survival in another.
  • YadC induced a mixed Th1/Th2 immune response with predominant pro-inflammatory cytokine production, distinct from LcrV's response.

Conclusions:

  • YadC represents a promising new target for developing vaccines against F1(-) Y. pestis strains.
  • The distinct immune response induced by YadC suggests a complementary or alternative mechanism of protection compared to LcrV.
  • Further research into YadC-based vaccines could enhance protection against pneumonic plague.

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