title: 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.
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, United States; Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555-0609, United States; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555-0609, United States; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-0609, United States. Electronic address: nathirum@utmb.edu.
authors.forename: Nagaraja R
authors.initials: NR
authors.lastname: Thirumalapura
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Crocquet-Valdes
authors.forename: Tais B
authors.initials: TB
authors.lastname: Saito
authors.forename: Sunil
authors.initials: S
authors.lastname: Thomas
authors.forename: Jere W
authors.initials: JW
authors.lastname: McBride
authors.forename: David H
authors.initials: DH
authors.lastname: Walker
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D004536:Ehrlichia / Q000235:genetics / Q000276:immunology*; D016873:Ehrlichiosis / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D017422:Sequence Analysis, DNA; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D004269:DNA, Bacterial; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D007371:Interferon-gamma
keywords: Antibody; Antigen; Ehrlichia; Intracellular bacteria; Protective immunity; Vaccine