Immunization with Ehrlichia P28 outer membrane proteins confers protection in a mouse model of ehrlichiosis

Patricia A. Crocquet-Valdes, Nagaraja R. Thirumalapura, Nahed Ismail, Xuejie Yu, Tais Saito, Heather Stevenson-Lerner, Colette A. Pietzsch, Sunil Thomas, David Walker

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Abstract

The obligately intracellular bacterium Ehrlichia chaffeensis that resides in mononuclear phagocytes is the etiologic agent of human monocytotropic ehrlichiosis (HME). HME is an emerging and often life-threatening, tick-transmitted infectious disease in the United States. Effective primary immune responses against Ehrlichia infection involve generation of Ehrlichia-specific gamma interferon (IFN-γ)-producing CD4 + T cells and cytotoxic CD8 + T cells, activation of macrophages by IFN-γ, and production of Ehrlichia-specific antibodies of the Th1 isotype. Currently, there are no vaccines available against HME. We evaluated the ability of 28-kDa outer membrane proteins (P28-OMP-1) of the closely related Ehrlichia muris to stimulate long-term protective memory T and B cell responses and confer protection in mice. The spleens of mice vaccinated with E. muris P28-9, P28-12, P28-19, or a mixture of these three P28 proteins (P28s) using a DNA prime-protein boost regimen and challenged with E. muris had significantly lower bacterial loads than the spleens of mock-vaccinated mice. Mice immunized with P28-9, P28-12, P28-19, or the mixture induced Ehrlichia-specific CD4 +Th1 cells. Interestingly, mice immunized with P28-14, orthologs of which in E. chaffeensis and E. canis are primarily expressed in tick cells, failed to lower the ehrlichial burden in the spleen. Immunization with the recombinant P28-19 protein alone also significantly decreased the bacterial load in the spleen and liver compared to those of the controls. Our study reports, for the first time, the protective roles of the Ehrlichia P28-9 and P28-12 proteins in addition to confirming previous reports of the protective ability of P28-19. Partial protection induced by immunization with P28-9, P28-12, and P28-19 against Ehrlichia was associated with the generation of Ehrlichia-specific cell-mediated and humoral immune responses.

Original languageEnglish (US)
Pages (from-to)2018-2025
Number of pages8
JournalClinical and Vaccine Immunology
Volume18
Issue number12
DOIs
StatePublished - Dec 2011

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Ehrlichia
Ehrlichiosis
Immunization
Membrane Proteins
T-cells
Proteins
Ehrlichia chaffeensis
Spleen
Aptitude
Bacterial Load
Macrophages
Ticks
T-Lymphocytes
Liver
Interferon-gamma
Bacteria
Vaccines
Chemical activation
Cells
Data storage equipment

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Immunology
  • Immunology and Allergy
  • Microbiology (medical)

Cite this

Immunization with Ehrlichia P28 outer membrane proteins confers protection in a mouse model of ehrlichiosis. / Crocquet-Valdes, Patricia A.; Thirumalapura, Nagaraja R.; Ismail, Nahed; Yu, Xuejie; Saito, Tais; Stevenson-Lerner, Heather; Pietzsch, Colette A.; Thomas, Sunil; Walker, David.

In: Clinical and Vaccine Immunology, Vol. 18, No. 12, 12.2011, p. 2018-2025.

Research output: Contribution to journalArticle

Crocquet-Valdes, Patricia A. ; Thirumalapura, Nagaraja R. ; Ismail, Nahed ; Yu, Xuejie ; Saito, Tais ; Stevenson-Lerner, Heather ; Pietzsch, Colette A. ; Thomas, Sunil ; Walker, David. / Immunization with Ehrlichia P28 outer membrane proteins confers protection in a mouse model of ehrlichiosis. In: Clinical and Vaccine Immunology. 2011 ; Vol. 18, No. 12. pp. 2018-2025.
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abstract = "The obligately intracellular bacterium Ehrlichia chaffeensis that resides in mononuclear phagocytes is the etiologic agent of human monocytotropic ehrlichiosis (HME). HME is an emerging and often life-threatening, tick-transmitted infectious disease in the United States. Effective primary immune responses against Ehrlichia infection involve generation of Ehrlichia-specific gamma interferon (IFN-γ)-producing CD4 + T cells and cytotoxic CD8 + T cells, activation of macrophages by IFN-γ, and production of Ehrlichia-specific antibodies of the Th1 isotype. Currently, there are no vaccines available against HME. We evaluated the ability of 28-kDa outer membrane proteins (P28-OMP-1) of the closely related Ehrlichia muris to stimulate long-term protective memory T and B cell responses and confer protection in mice. The spleens of mice vaccinated with E. muris P28-9, P28-12, P28-19, or a mixture of these three P28 proteins (P28s) using a DNA prime-protein boost regimen and challenged with E. muris had significantly lower bacterial loads than the spleens of mock-vaccinated mice. Mice immunized with P28-9, P28-12, P28-19, or the mixture induced Ehrlichia-specific CD4 +Th1 cells. Interestingly, mice immunized with P28-14, orthologs of which in E. chaffeensis and E. canis are primarily expressed in tick cells, failed to lower the ehrlichial burden in the spleen. Immunization with the recombinant P28-19 protein alone also significantly decreased the bacterial load in the spleen and liver compared to those of the controls. Our study reports, for the first time, the protective roles of the Ehrlichia P28-9 and P28-12 proteins in addition to confirming previous reports of the protective ability of P28-19. Partial protection induced by immunization with P28-9, P28-12, and P28-19 against Ehrlichia was associated with the generation of Ehrlichia-specific cell-mediated and humoral immune responses.",
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