Recombinant Ehrlichia P29 protein induces a protective immune response in a mouse model of ehrlichiosis

Abstract

Ehrlichioses are emerging tick-borne bacterial diseases of humans and animals for which no vaccines are available. The diseases are caused by obligately intracellular bacteria belonging to the genus Ehrlichia. Several immunoreactive proteins of ehrlichiae have been identified based on their reactivity with immune sera from human patients and animals. These include the major outer membrane proteins, ankyrin repeat proteins and tandem repeat proteins (TRP). Polyclonal antibodies directed against the tandem repeats (TRs) of Ehrlichia chaffeensis TRP32, TRP47 and TRP120 have been shown to provide protection in mice. In the present study, we evaluated E. muris P29, which is the ortholog of E. chaffeensis TRP47 and E. canis TRP36, as a subunit vaccine in a mouse model of ehrlichiosis. Our study indicated that unlike E. chaffeensis TRP47 and E. canis TRP36, orthologs of E. muris (P29) and E. muris-like agent (EMLA) do not contain tandem repeats. Immunization of mice with recombinant E. muris P29 induced significant protection against a challenge infection. The protection induced by E. muris P29 was associated with induction of strong antibody responses. In contrast to development of P29-specific IgG antibodies following immunization, development of P29-specific IgG antibodies, but not IgM antibodies, was impaired during persistent E. muris infection. Furthermore, our study indicated that CD4+ T cells target P29 during E. muris infection and differentiate into IFN-γ-producing Th1 effector/memory cells. In conclusion, our study indicated that orthologs of E. muris P29 showed considerable variation in the central tandem repeat region among different species, induction of P29-specific IgG antibody response was impaired during persistent E. muris infection, and rP29 induced protective immune responses.

Attenuated Mutants of Ehrlichia chaffeensis Induce Protection against Wild-Type Infection Challenge in the Reservoir Host and in an Incidental Host

“…A DNA vaccine targeting a p28 outer membrane protein homolog (MAP1) in another Ehrlichia species, E. ruminantium, also confers partial protection against infection challenges (16). Similarly, recent studies described that p28 outer membrane proteins of E. muris stimulate mouse memory B and T cell responses, reducing the bacterial burden after 10 to 14 days postchallenge with wild-type infection (17,18). Several studies of Ehrlichia species also demonstrated that attenuated strains offer a high level of protection.…”

Efficacy and Immune Correlates of OMP-1B and VirB2-4 Vaccines for Protection of Dogs from Tick Transmission of Ehrlichia chaffeensis

“…In this study, two animal models were used: mouse-intraperitoneal inoculation and dog-tick transmission models. Although the mouse infection model is unnatural, most vaccine studies on vector-borne obligatory intracellular bacteria have been carried out in mice challenged by needle inoculation ( 54 ) and almost all Ehrlichia pathogenesis and immunologic research used this model to derive immunologic or other signatures of responses ( 55 – 58 ). Dog-tick transmission is the natural mode of transmission.…”

Immune Response to Tick-Borne Hemoparasites: Host Adaptive Immune Response Mechanisms as Potential Targets for Therapies and Vaccines

“…Other Ehrlichia immune-reactive identified antigens include ferric ion-binding protein, disulfide bond formation protein, ankyrin repeat proteins (i.e., E. canis gp200), and tandem repeat proteins (TRP-) [ 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. Several orthologs of TRPs have been discovered in E. chaffeensis and E. canis —for example, TRP120/TRP140, TRP75/TRP95, TRP47/TRP36 and TRP32/TRP19 [ 40 ]. Through interaction with several host proteins, TRPs contribute to the infection establishment.…”

“…A recently identified E. muris TRP, P29, recognized as the ortholog E. chaffeensis TRP47 and E. canis TRP36, was found to generate a strong IgG antibody response and to stimulate CD4 + T cell differentiation into IFN-γ-producing Th1 effector/memory cells, activating macrophage microbicide activity. These effects suggest a possible inclusion for E. muris P29 in a subunit vaccine against ehrlichiosis [ 40 ].…”