Protective DNA immunization against Chlamydia pneumoniae.
We have investigated the efficacy of the DNA vaccination using the heat shock protein 60 (HSP-60) gene of C. pneumoniae, for protection of mice against 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 plasmids (p) encoding pHSP-60. The reduction of the bacterial load coincided with a decreased severity of disease. No specific antibodies were detected after protective i. n. immunization. In contrast, mice immunized intradermally (i.d.) were not protected against challenge with C. pneumoniae, although specific humoral Immunoglobulin (Ig)G responses were generated. Co-inoculation i.n. of pHSP-60 with pIL-12 but not with pGM-CSF further increased protection of mice against infection with C. pneumoniae. Lungs from pHSP-60 i.n. immunized and infected mice showed higher levels of interferon (IFN)-gamma mRNA, and spleen cells from these mice co-cultured with r-HSP-60 released higher 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. Likewise, 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 absence of CD8+ T cells, were involved in worsening the outcome of infection. This worsening was linked with a shift towards a Th2 cytokine pattern.
Svanholm
C
C
Microbiology and Tumorbiology Center, Department of Pathology, Karolinska Institute, Stockholm, Sweden.
Bandholtz
L
L
Castaños-Velez
E
E
Wigzell
H
H
Rottenberg
M E
ME
D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016993:Chlamydophila pneumoniae / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D015169:Colony Count, Microbial; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000032:analysis; D007371:Interferon-gamma / Q000008:administration & dosage / Q000235:genetics; D018664:Interleukin-12 / Q000008:administration & dosage; D008168:Lung / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009297:Nasal Mucosa / Q000276:immunology; D010957:Plasmids; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000378:metabolism; D019444:Vaccines, DNA / Q000008:administration & dosage*
D000907:Antibodies, Bacterial; D018834:Chaperonin 60; D007074:Immunoglobulin G; D012333:RNA, Messenger; D019444:Vaccines, DNA; D018664:Interleukin-12; D007371:Interferon-gamma