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Novel Chlamydia muridarum T Cell Antigens Induce Protective Immunity against Lung and Genital Tract Infection in Murine Models¹

British Columbia Centre for Disease Control, University of British Columbia, Vancouver, British Columbia, Canada

Using a combination of affinity chromatography and tandem mass spectrometry, we recently identified 8 MHC class II (I-A^b) -bound Chlamydia peptides eluted from dendritic cells (DCs) infected with Chlamydia muridarum. In this study we cloned and purified the source proteins that contained each of these peptides and determined that three of the eight peptide/protein Ags were immunodominant (PmpG-1, RplF, and PmpE/F-2) as identified by IFN- ELISPOT assay using splenocytes from C57BL/6 mice recovered from C. muridarum infection. To evaluate whether the three immunodominant Chlamydia protein Ags were also able to protect mice against Chlamydia infection in vivo, we adoptively transferred LPS-matured DCs transfected ex vivo with the cationic liposome DOTAP (N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate) and individual PmpG-1(25–500aa), RplF, or PmpE/F-2 (25–575 aa) proteins. The results showed that the transfected Chlamydia proteins were efficiently delivered intracellularly into DCs. Mice vaccinated with DCs transfected with individual Chlamydia protein PmpG-1_25–500, RplF, or PmpE/F-2_25–575 exhibited significant resistance to challenge infection as indicated by reduction in the median Chlamydia inclusion forming units in both the lung and genital tract models. The major outer membrane protein was used as a reference Ag but conferred significant protection only in the genital tract model. Overall, vaccination with DCs transfected with PmpG-1_25–500 exhibited the greatest degree of protective immunity among the four Chlamydia Ags tested. This study demonstrates that T cell peptide Ags identified by immunoproteomics can be successfully exploited as T cell protein-based subunit vaccines and that PmpG-1_25–500 protein may be a suitable vaccine candidate for further evaluation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from Canadian Institutes of Health Research and National Institutes of Health (Grant no. R01AI076483).

² Address correspondence and reprint requests to Dr. Robert C. Brunham, British Columbia Centre for Disease Control, 655 West 12th Avenue, Vancouver, British Columbia V5Z 4R4, Canada. E-mail address: robert.brunham{at}bccdc.ca

³ Abbreviations used in this paper: MOMP, major outer membrance protein; CMI, cell-mediated immune response; DC, dendritic cell; DOTAP, N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate; EB, elementary body; HK-EB, heat-killed EB; DAB, diaminobenzidine; IFU, inclusion-forming unit.