Publikation
Enhanced protection against viral infection by co-administration of plasmid DNA coding for viral antigen and cytokines in mice
Wissenschaftlicher Artikel/Review - 01.06.1999
Operschall E, Schuh T, Heinzerling Lucie, Pavlovic J, Moelling K
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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. STUDY DESIGN: 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.