TY - JOUR
T1 - Recombinant Ehrlichia P29 protein induces a protective immune response in a mouse model of ehrlichiosis
AU - Thirumalapura, Nagaraja R.
AU - Crocquet-Valdes, Patricia A.
AU - Saito, Tais B.
AU - Thomas, Sunil
AU - McBride, Jere W.
AU - Walker, David H.
N1 - Funding Information:
We thank Tahereh Dadfarnia and Beau DiCicco for their help with cloning and expression of the recombinant protein. A part of this study was supported by grant AI31431 from the National Institute of Allergy and Infectious Diseases to DHW. NRT is supported by an NIAID Research Scholar Development Award (5K22AI089973). The excellent secretarial assistance by Rachel Stella is gratefully acknowledged.
PY - 2013/12/5
Y1 - 2013/12/5
N2 - 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.
AB - 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.
KW - Antibody
KW - Antigen
KW - Ehrlichia
KW - Intracellular bacteria
KW - Protective immunity
KW - Vaccine
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UR - http://www.scopus.com/inward/citedby.url?scp=84887607120&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2013.10.036
DO - 10.1016/j.vaccine.2013.10.036
M3 - Article
C2 - 24144475
AN - SCOPUS:84887607120
SN - 0264-410X
VL - 31
SP - 5960
EP - 5967
JO - Vaccine
JF - Vaccine
IS - 50
ER -