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Infection and Immunity, November 2007, p. 5453-5459, Vol. 75, No. 11
0019-9567/07/$08.00+0     doi:10.1128/IAI.00713-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

CD4 T-Cell Epitopes Associated with Protective Immunity Induced following Vaccination of Mice with an Ehrlichial Variable Outer Membrane Protein{triangledown} ,{dagger}

Bisweswar Nandi,1 Kathryn Hogle,1 Nicholas Vitko,1 and Gary M. Winslow1,2*

Wadsworth Center, New York State Department of Health, P.O. Box 22002, Albany, New York 12201-2002,1 Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, New York 12201-05092

Received 25 May 2007/ Returned for modification 16 July 2007/ Accepted 1 August 2007

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-19107-122. 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-19107-122 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.

* Corresponding author. Mailing address: Wadsworth Center, 120 New Scotland Avenue, Albany, NY 12208. Phone: (518) 473-2795. Fax: (518) 486-9858. E-mail: gary.winslow{at}wadsworth.org

{triangledown} Published ahead of print on 13 August 2007.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: R. P. Morrison

Infection and Immunity, November 2007, p. 5453-5459, Vol. 75, No. 11
0019-9567/07/$08.00+0     doi:10.1128/IAI.00713-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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