DNA vaccination using coexpression of cytokine genes with a bacterial gene encoding a 60-kDa heat shock protein.
Coexpression of cytokine genes together with antigen-encoding genes in DNA vaccination vectors can increase humoral and cellular immune responses and may steer them in a Th1 or Th2 direction. In this study, the modulatory effect of interleukin (IL)-2, IL-4, and interferon (IFN)-gamma coexpressed with the 60-kDa heat shock protein (Hsp60) of Yersinia enterocolitica O:8 (Y-Hsp60) was studied. DNA vaccination with gamma-hsp60 evoked specific humoral and cellular immune responses as well as reduction of the splenic bacterial load upon challenge with Y. enterocolitica in a mouse infection model. Coexpression of IL-2 or IFN-gamma enhanced Y. enterocolitica-specific total IgG (P < 0.05) and IgG2a antibody responses. Coexpression of IFN-gamma also improved the proliferative T cell responses upon stimulation with Y-Hsp60. A reduction of the splenic bacterial load as compared with the plasmid encoding Y-Hsp60 only was found for the IFN-gamma coexpressing vector. Thus, coexpression of cytokine genes such as IFN-gamma in DNA vaccination vectors might improve immunity and help to overcome the side effects of standard adjuvants.
Hornef
M W
MW
Max von Pettenkofer Institute for Hygiene and Medical Microbiology, LMU Munich, Germany. mathias.hornef@mtc.ki.se
Noll
A
A
Schirmbeck
R
R
Reimann
J
J
Autenrieth
I B
IB
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000276:immunology; D018834:Chaperonin 60 / Q000235:genetics* / Q000276:immunology*; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010957:Plasmids; D013154:Spleen / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D015009:Yersinia Infections / Q000276:immunology* / Q000382:microbiology; D015008:Yersinia enterocolitica / Q000254:growth & development / Q000276:immunology*
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D018834:Chaperonin 60; D016207:Cytokines; D007376:Interleukin-2; D019444:Vaccines, DNA; D015847:Interleukin-4; D007371:Interferon-gamma