Modulation of immune responses induced by DNA vaccine expressing glycoprotein B of Pseudorabies Virus via coadministration of IFN-gamma-associated cytokines.
The immunomodulatory efficacy of interferon-gamma (IFN-gamma)-associated cytokines coadministered with a plasmid DNA vaccine has been investigated, with variable results. Therefore, to test the immunomodulatory effect of IFN-gamma-associated cytokines as vaccine adjuvant, the present study evaluated the immune responses induced by pseudorabies virus (PrV) gB-encoded plasmid DNA vaccine coadministered with IFN-gamma-associated cytokines and chemokines. These cytokines and chemokines included interleukin-12 (IL-12) and IL-18, as potent inducers of IFN-gamma, and IFN-gamma-inducible protein (IP-10), the production of which is IFN-gamma dependent. A coinjection of either IL-12 or IL-18 strongly suppressed the humoral antibody responses but increased the production of the Th1-type cytokines IFN-gamma and IL-2 from immune T cells. Such antibody suppression was closely related to the increased susceptibility against a virulent viral challenge. On the other hand, IP-10 exhibited enhanced immune responses in both antibody responses and IFN-gamma production of immune T cells and facilitated the prolonged survival of infected mice. In contrast, there was no significant change in the immune responses of the mice that received codelivery of IFN-gamma. Therefore, IFN-gamma-associated cytokines, as Th1-type inducers, can generate unexpected and unwanted effects, and their application as a vaccine adjuvant should be carefully evaluated depending on the target antigens.
Yoon
Hyun A
HA
College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Jeonju 561-756, Republic of Korea.
Aleyas
Abi G
AG
George
Junu A
JA
Park
Seong Ok
SO
Han
Young Woo
YW
Lee
John Hwa
JH
Kang
Ho Young
HY
Kang
Seong Ho
SH
Cho
Jeong Gon
JG
Eo
Seong Kug
SK
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D011558:Herpesvirus 1, Suid / Q000276:immunology*; D022283:Herpesvirus Vaccines / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D011557:Pseudorabies / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism
D000914:Antibodies, Viral; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines; D022283:Herpesvirus Vaccines; D020382:Interleukin-18; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C070915:glycoprotein gII, pseudorabies virus; D018664:Interleukin-12; D007371:Interferon-gamma