Yersinia pestis YopE contains a dominant CD8 T cell epitope that confers protection in a mouse model of pneumonic plague

Jr Shiuan Lin, Frank M. Szaba, Lawrence W. Kummer, Brett A. Chromy, Stephen T. Smiley

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Septic bacterial pneumonias are a major cause of death worldwide. Several of the highest priority bioterror concerns, including anthrax, tularemia, and plague, are caused by bacteria that acutely infect the lung. Bacterial resistance to multiple antibiotics is increasingly common. Although vaccines may be our best defense against antibiotic-resistant bacteria, there has been little progress in the development of safe and effective vaccines for pulmonary bacterial pathogens. The Gram-negative bacterium Yersinia pestis causes pneumonic plague, an acutely lethal septic pneumonia. Historic pandemics of plague caused millions of deaths, and the plague bacilli's potential for weaponization sustains an ongoing quest for effective countermeasures. Subunit vaccines have failed, to date, to fully protect nonhuman primates. In mice, they induce the production of Abs that act in concert with type 1 cytokines to deliver high-level protection; however, the Y. pestis Ags recognized by cytokine-producing T cells have yet to be defined. In this study, we report that Y. pestis YopE is a dominant Ag recognized by CD8 T cells in C57BL/6 mice. After vaccinating with live attenuated Y. pestis and challenging intranasally with virulent plague, nearly 20% of pulmonary CD8 T cells recognize this single, highly conserved Ag. Moreover, immunizing mice with a single peptide, YopE 69-77, suffices to confer significant protection from lethal pulmonary challenge. These findings suggest YopE could be a valuable addition to subunit plague vaccines and provide a new animal model in which sensitive, pathogen-specific assays can be used to study CD8 T cell-mediated defense against acutely lethal bacterial infections of the lung.

Original languageEnglish (US)
Pages (from-to)897-904
Number of pages8
JournalJournal of Immunology
Volume187
Issue number2
DOIs
StatePublished - Jul 15 2011
Externally publishedYes

Fingerprint

Yersinia pestis
T-Lymphocyte Epitopes
Plague
Lung
T-Lymphocytes
Subunit Vaccines
Plague Vaccine
Bacterial Vaccines
Cytokines
Anti-Bacterial Agents
Bacteria
Tularemia
Bacterial Pneumonia
Anthrax
Pandemics
Gram-Negative Bacteria
Inbred C57BL Mouse
Bacterial Infections
Bacillus
Primates

ASJC Scopus subject areas

  • Immunology

Cite this

Yersinia pestis YopE contains a dominant CD8 T cell epitope that confers protection in a mouse model of pneumonic plague. / Lin, Jr Shiuan; Szaba, Frank M.; Kummer, Lawrence W.; Chromy, Brett A.; Smiley, Stephen T.

In: Journal of Immunology, Vol. 187, No. 2, 15.07.2011, p. 897-904.

Research output: Contribution to journalArticle

Lin, Jr Shiuan ; Szaba, Frank M. ; Kummer, Lawrence W. ; Chromy, Brett A. ; Smiley, Stephen T. / Yersinia pestis YopE contains a dominant CD8 T cell epitope that confers protection in a mouse model of pneumonic plague. In: Journal of Immunology. 2011 ; Vol. 187, No. 2. pp. 897-904.
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