Enhanced protection against viral infection by co-administration of plasmid DNA coding for viral antigen and cytokines in mice.
BACKGROUND
DNA vaccines have been shown to induce protective immunity against viral infections in different animal models. We have recently demonstrated that DNA vaccine induced protective immunity against influenza A virus and La Crosse virus (LACV) is primarily mediated by humoral immune response.


OBJECTIVE
The goal of this study was to investigate whether administration of DNA coding for cytokines such as interleukin 12 (IL-12) and granulocyte-macrophage colony-stimulating factor (GM-CSF) could increase the protective immune response induced by vaccination with DNA coding for viral antigens.


METHODS
For the influenza A virus or LACV model, C57BL/6 or interferon-alpha/beta receptor (IFNAR-1)-deficient mice, respectively, were vaccinated once or twice with 100 micrograms of DNA encoding viral antigens. At the same time plasmid DNAs (100 micrograms) coding either for mouse GM-CSF or mouse IL-12 were administered. The mice were subsequently challenged with a lethal dose of influenza A virus or LACV and monitored for clinical symptoms (weight loss) and survival.


RESULTS
To achieve a high degree of protection (70% survival) two injections of DNA encoding the influenza A virus surface protein hemagglutinin (HA) were required. Intriguingly, administration of DNA coding for IL-12 alone also led to a pronounced protective effect against virus challenge. Co-administration of DNAs encoding IL-12 and HA significantly increased the protective immunity against influenza A virus, while IL-12 expression did not improve protection upon vaccination with DNA coding for the internal nucleocapsid protein N of LACV. Co-injection of DNA coding for mouse GM-CSF and HA also showed an adjuvant effect.


CONCLUSIONS
The data clearly indicate that co-administration of DNA encoding cytokines such as IL-12 and GM-CSF with DNA coding for viral antigens has adjuvant effects on the protective immune response against different viral pathogens.
Institute of Medical Virology, University of Zurich, Switzerland.
E
E
Operschall
T
T
Schuh
L
L
Heinzerling
J
J
Pavlovic
K
K
Moelling
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D006224:Cricetinae; D004279:DNA, Viral / Q000276:immunology; D004670:Encephalitis, California / Q000517:prevention & control*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D018062:La Crosse virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000276:immunology*; D010957:Plasmids / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
D000956:Antigens, Viral; D004279:DNA, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019590:Nucleocapsid Proteins; D019444:Vaccines, DNA; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor