This thesis describes DNA-based vaccination and the importance of bacterial DNA in different immunological perspectives. Intranasal (i.n.) DNA vaccination utilizing a plasmid encoding the chlamydial heat shock protein 60 (p-hsp-60) generated lower bacterial burden and reduced pathology in the lungs of mice after subsequent infection with C. pneumoniae. This DNA vaccine- induced protection was dependent on T cells and induction of IFN-gamma. Co-administration of a plasmid encoding IL-12 ftirther enhanced the protective effect of the DNA vaccine. Interestingly, in the absence of CD8 T cells, CD4 T cells induced by the p-hsp-60 DNA vaccine were involved in deteriorating the outcome of infection. This detrimental response was linked to a shift towards a Th2 cytokine profile in the lungs. In. DNA vaccination using the chlamydial outer membrane protein 2 (OMP- 2) combined with a CTLA-4 expression system also generated reduction of bacterial load in mouse lung after C. pneumoniae infection compared to controls. In contrast, subcutaneous (s.c.) OMP-2 protein-based immunization in Freund's complete adjuvant (FCA) generated increased lung bacterial load, with increased disease severity. This pathological outcome of disease was dependent on T cells and associated with a Th2 immune response. When oligodeoxynucleotides containing CpG motifs mixed with Freund's incomplete adjuvant (FIA- CpG ODN) were used as adjuvant this detrimental response was shifted towards partial protection against infection. This partial protection was linked to a Th1 type of immune response. In an approach to identify protein(s) that are included in CpG DNA stimulation, an isolation procedure was developed for a crude protein extract prepared from peripheral blood mononuclear cells (PBMC). The binding between the protein(s) and CpG ODN in the extract was followed by electromobility shift assay (EMSA) analysis. Using a Series of different chromatographic purification steps and protein sequence analysis, heat shock protein 90 (hsp90) was identified as ...