Comparative analysis of effects of cytokine gene adjuvants on DNA vaccination against Mycobacterium tuberculosis heat shock protein 65.
DNA-based vaccines generate potent cellular immunity as well as humoral immunity. It seems evident that cytokines play a crucial role in generation of effector T cell subsets and in determining the magnitude of the response by DNA vaccines. In this study, we compared the effects of several TH1 cytokine genes as adjuvant in DNA vaccination using mycobacterial Hsp65 as a model antigen. Our results demonstrated that although the overall immune response to Hsp65 was enhanced by co-injection of Hsp65 DNA with cytokine genes, each cytokine gene was shown to affect different immune response elements. Co-injection of Hsp65 DNA with IL-12 or GM-CSF led to an increase in IFN-gamma production and represented potent protections against Mycobacterium tuberculosis challenge, while that with Eta-1, IL-12 or IL-18 gene led to an elevated IgG2a/IgG1 ratio. Interestingly, co-administration of Flt3L gene was shown to enhance the Ag-specific CTL response. These results show that the direction and magnitude of immune response in DNA vaccination against Hsp65 of M. tuberculosis could be modulated in different ways by co-injection of an appropriate cytokine gene as adjuvant.
Baek
Kyoung Min
KM
Laboratory of Immunology and Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Shillimdong, Kwanakgu, Seoul 151-742, South Korea.
Ko
Sung-Youl
SY
Lee
Mira
M
Lee
Joong-Seok
JS
Kim
Jae-Ouk
JO
Ko
Hyun-Jeong
HJ
Lee
Jae-Woo
JW
Lee
Sang-Hoon
SH
Cho
Sang-Nae
SN
Kang
Chang-Yuil
CY
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity; D001426:Bacterial Proteins / Q000276:immunology*; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology*; D002860:Chromium Radioisotopes; D015169:Colony Count, Microbial; D016207:Cytokines / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000382:microbiology / Q000517:prevention & control; D019444:Vaccines, DNA / Q000276:immunology
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D018834:Chaperonin 60; D002860:Chromium Radioisotopes; D016207:Cytokines; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; C074119:heat-shock protein 65, Mycobacterium; D018664:Interleukin-12; D007371:Interferon-gamma; D018833:Chaperonins