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.