title: CD4 T-cell epitopes associated with protective immunity induced following vaccination of mice with an ehrlichial variable outer membrane protein.
abstract: The ehrlichiae express variable outer membrane proteins (OMPs) that play important roles in both pathogenesis and host defense. Previous studies revealed that OMPs are immunodominant B-cell antigens and that passive transfer of anti-OMP antibodies can protect SCID mice from fatal ehrlichial infection. In this study, we used a model of fatal monocytotropic ehrlichiosis caused by Ehrlichia bacteria from Ixodes ovatus (IOE) to determine whether OMP immunization could generate protective immunity in immunocompetent mice. Immunization of C57BL/6 mice with a purified recombinant OMP expressed by IOE omp19 generated protection from fatal IOE infection and elicited robust humoral and CD4 T-cell responses. To identify CD4 T-cell epitopes within OMPs, we performed enzyme-linked immunospot analyses for gamma interferon (IFN-gamma) production using a panel of overlapping 16-mer peptides from IOE OMP-19. Five immunoreactive peptides comprising residues 30 to 45, 77 to 92, 107 to 122, 197 to 212, and 247 to 264 were identified; the strongest response was generated against OMP-19(107-122). Most of the peptides are conserved between E. muris and E. chaffeensis OMP-19, and they elicited IFN-gamma production in CD4 T cells from E. muris-infected mice, indicating that T-cell epitope cross-reactivity likely contributes to heterologous immunity. Accordingly, CD4 T-cell responses to both OMP-19 and OMP-19(107-122) were of greater magnitude following high-dose IOE challenge of mice that had been immunized by prior infection with E. muris. Our studies cumulatively identify B- and T-cell epitopes that are associated with protective homologous and heterologous immunity during ehrlichial infection.
authors: Wadsworth Center, 120 New Scotland Avenue, Albany, NY 12208, USA.
authors: Bisweswar
authors: B
authors: Nandi
authors: Kathryn
authors: K
authors: Hogle
authors: Nicholas
authors: N
authors: Vitko
authors: Gary M
authors: GM
authors: Winslow
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015169:Colony Count, Microbial; D004536:Ehrlichia / Q000276:immunology* / Q000302:isolation & purification; D016873:Ehrlichiosis / Q000276:immunology* / Q000517:prevention & control*; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D018884:Ixodes / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D007371:Interferon-gamma
references: Infect Immun. 2000 Apr;68(4):2187-95
references: 10722619
references: J Immunol. 2004 Jun 1;172(11):6894-901
references: 15153508
references: J Immunol. 2001 Jan 15;166(2):1114-24
references: 11145692
references: J Immunol. 2001 Feb 1;166(3):1855-62
references: 11160232
references: Infect Immun. 2001 Apr;69(4):2083-91
references: 11254561
references: J Immunol. 2002 Aug 1;169(3):1419-25
references: 12133967
references: Am J Pathol. 2004 Sep;165(3):997-1006
references: 15331423
references: J Immunol Methods. 1995 Apr 12;181(1):45-54
references: 7537312
references: J Exp Med. 1996 Oct 1;184(4):1549-54
references: 8879228
references: Infect Immun. 1998 Jan;66(1):132-9
references: 9423849
references: J Immunol Methods. 1998 Mar 15;212(2):187-92
references: 9672206
references: Infect Immun. 1998 Nov;66(11):5406-13
references: 9784551
references: Infect Immun. 2004 Dec;72(12):7360-6
references: 15557669
references: Infect Immun. 2005 Jan;73(1):79-87
references: 15618143
references: Infect Immun. 2005 Dec;73(12):8009-16
references: 16299294
references: Infect Immun. 2006 Mar;74(3):1846-56
references: 16495559
references: J Immunol. 2006 Oct 1;177(7):4644-51
references: 16982903
references: Infect Immun. 2007 May;75(5):2333-42
references: 17339347
references: J Immunol. 2003 Apr 1;170(7):3790-8
references: 12646645
references: Infect Immun. 2004 Jan;72(1):159-67
references: 14688093
references: J Immunol. 2004 Feb 1;172(3):1786-800
references: 14734762
references: J Clin Microbiol. 2000 Apr;38(4):1331-8
references: 10747103