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 agai nst viral infections in different animal models. We have recently demonstra ted 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 administrati on of DNA coding for cytokines such as interleukin 12 (IL-12) and granulocy te-macrophage colony-stimulating factor (GM-CSF) could increase the protect ive immune response induced by Vaccination with DNA coding for viral antige ns. Study design: For the influenza A virus or LACV model, C57BL/6 or inter feron-alpha/beta receptor (IFNAR-l)-deficient mice, respectively, were vacc inated once or twice with 100 mu g of DNA encoding viral antigens. At the s ame time plasmid DNAs (100 mu g) coding either for mouse GM-CSF of 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 (weig ht loss) and survival. Results: To achieve a high degree of protection (70% survival) two injections of DNA encoding the influenza A virus surface pro tein 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 significan tly increased the protective immunity against influenza A virus, while IL-1 2 expression did not improve protection upon Vaccination with DNA coding fo r the internal nucleocapsid protein N of LACV. Go-injection of DNA coding f or mouse GM-CSF and HA also showed an adjuvant effect. Conclusions: The dat a 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 o n the protective immune response against different viral pathogens. (C) 199 9 Elsevier Science B.V. All rights reserved.