Protective DNA immunization against Chlamydia pneumoniae

We have investigated the efficacy of the DNA vaccination using the heat sho ck protein 60 (HSP-60) gene of C. pneumoniae, for protection of mice agains t infection with the bacteria. C57Bl/6 mice had a 5-20-fold reduction of C. pneumoniae numbers in lungs when immunized intranasally (i.n.) with plasmi ds (p) encoding pHSP-60. The reduction of the bacterial load coincided with a decreased severity of disease. No specific antibodies were detected afte r protective i.n. immunization. In contrast, mice immunized intradermally ( i.d.) were not protected against challenge with C. pneumoniae, although spe cific humoral Immunoglobulin (Ig)G responses were generated. Co-inoculation i.n. of pHSP-60 with pIL-12 but not with pGM-CSF further increased protect ion of mice against infection with C. pneumoniae. Lungs from pHSP-60 i.n. i mmunized and infected mice showed higher levels of interferon (IFN)-gamma m RNA, and spleen cells from these mice co-cultured with r-HSP-60 released hi gher levels of IFN-gamma and displayed higher proliferative responses than nonimmunized and infected controls. pHSP-60 immunized IFN-gamma receptor (R )(-/-) mice were not protected against infection with C. pneumoniae. Likewi se, i.n. administration of pIFN-gamma alone induced significant protection. DNA vaccine-induced protection was CD4(+) and CD8(+) T-cell dependent, as shown by DNA-vaccination of MHC class II-/-, CD4(-/-), CD8(-/-) and CD4(-/- )CD8(-/-) mice. Interestingly, DNA vaccine induced CD4(+) T cells, in the a bsence of CD8(+) T cells, were involved in worsening the outcome of infecti on. This worsening was linked with a shift towards a Th2 cytokine pattern.