A T cell epitope-based vaccine protects against chlamydial infection in HLA-DR4 transgenic mice

作者：Li Weidang; Murthy Ashlesh K; Lanka Gopala Krishna; Chetty Senthilnath L; Yu Jieh Juen; Chambers James P; Zhong Guangming; Forsthuber Thomas G; Guentzel M Neal; Arulanandam Bernard P^*

来源：Vaccine, 2013, 31(48): 5722-5728.

DOI：10.1016/j.vaccine.2013.09.036

• Chlamydia
• rCPAF
• Tetramer
• T cell epitopes
• HLA-DR4 transgenic mice
• Detection of antigen specific T cells

Vaccination with recombinant chlamydial protease-like activity factor (rCPAF) has been shown to provide robust protection against genital Chlamydia infection. Adoptive transfer of IFN-gamma competent CPAF-specific CD4(+) T cells was sufficient to induce early resolution of chlamydial infection and reduction of subsequent pathology in recipient IFN-gamma-deficient mice indicating the importance of IFN-gamma secreting CD4(+) T cells in host defense against Chlamydia. In this study, we identify CD4(+) T cell reactive CPAF epitopes and characterize the activation of epitope-specific CD4(+) T cells following antigen immunization or Chlamydia challenge. Using the HLA-DR4 (HLA-DRB1*0401) transgenic mouse for screening overlapping peptides that induced T cell IFN-gamma production, we identified at least 5 CPAF T cell epitopes presented by the HLA-DR4 complex. Immunization of HLA-DR4 transgenic mice with a rCPAFep fusion protein containing these 5 epitopes induced a robust cell-mediated immune response and significantly accelerated the resolution of genital and pulmonary Chlamydia infection. rCPAFep vaccination induced CPAF-specific CD4(+) T cells in the spleen were detected using HLA-DR4/CPAF-epitope tetramers. Additionally, CPAF-specific CD4(+) clones could be detected in the mouse spleen following Chlamydia muridarum and a human Chlamydia trachomatis strain challenge using these novel tetramers. These results provide the first direct evidence that a novel CPAF epitope vaccine can provide protection and that HLA-DR4/CPAF-epitope tetramers can detect CPAF epitope-specific CD4(+) T cells in HLA-DR4 mice following C muridarum or C. trachomatis infection. Such tetramers could be a useful tool for monitoring CD4(+) T cells in immunity to Chlamydia infection and in developing epitope-based human vaccines using the murine model.

• 出版日期2013-11-19