Enhanced protection against viral infection by co-administration of plasmid DNA coding for viral antigen and cytokines in mice

Operschall, Elisabeth; Schuh, Theda; Heinzerling, Lucie; Pavlovic, Jovan; Moelling, Karin

doi:10.1016/s1386-6532(99)00008-6

Cited by 37 publications

(25 citation statements)

References 43 publications

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“…By contrast, vaccination with plasmid DNA encoding the internal nucleocapsid protein (pVR1012-N) showed at best a partial effect after three immunizations (30% survival). These results are reminiscent of data obtained with nucleocapsid proteins of other viruses like influenza A virus and hantavirus where no or weak protective effects were seen despite the induction of humoral and cellular immune responses [2,19,26,40]. At first glance these findings may be unexpected, but they can be explained by two different mechanisms.…”

Section: Discussionsupporting

confidence: 69%

DNA Vaccination against La Crosse Virus

Pavlovic

Schultz²,

Hefti³

et al. 2000

Intervirology

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For the development of effective conventional vaccines or DNA vaccines against viruses, the availability of suitable animal models is an essential prerequisite. For many recently emerging zoonotic viruses, suitable animal models are still missing. We have established a novel small animal model for DNA vaccines using mice lacking a functional interferon-α/β receptor (IFNAR-1). IFNAR-1-deficient mice are highly susceptible to many different viruses despite their ability to mount a normal humoral and cellular immune response. Taking advantage of this animal model, we show that mice can be completely protected from lethal challenge with a single injection of plasmid DNA encoding the viral envelope proteins G1 and G2. By contrast, vaccination with a plasmid encoding the internal nucleocapsid protein N had little effect. In an effort to enhance the protective immune response to N we assessed the efficacy of vaccination with plasmid DNA encoding N in combination with a plasmid encoding the cytokine IL-12 as adjuvant. IL-12 enhanced the survival of mice following viral challenge, but the effect was independent of N indicating the involvement of components of the innate immune system such as NK cells.

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Section: Discussionsupporting

confidence: 69%

DNA Vaccination against La Crosse Virus

Pavlovic

Schultz²,

Hefti³

et al. 2000

Intervirology

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“…These results may support the hypothesis that in IFNreceptor ±deficient mice APCs cannot be activated by IFN -to produce IL-12. Finally, (4 ) The results propose that IL -12 expressed from plasmid DNA initiates the positive feedback system, thereby directing the immune response to the Th1 development. The early triggering of the cellular immune response appears to be important for the antimetastatic efficiency of IL -12 DNA treatment.…”

Section: Discussionmentioning

confidence: 98%

Induction of long-lasting cytokine effect by injection of IL-12 encoding plasmid DNA

et al. 2000

Self Cite

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We have recently demonstrated that DNA coding for both subunits of the murine IL -12 heterodimer exhibits a strong antimetastatic effect against B16 -melanoma in C57BL / 6 mice and after intratumoral injection tumor regression. Here we show that the antimetastatic effect can be detected when the DNA is injected intramuscularly 30 days before tumor cell challenge. A long -term IL -12 expression was measured for up to 50 days in the serum with a peak at day 20 amounting to about 10 ng / mL in C57BL / 6 mice. CpG oligodeoxynucleotides also induce IL -12 expression, however, only for a few hours. IL -12 DNA administration induces longlasting systemic IFN -production, whereas IL -4 and TNF -levels remained undetectable. NK cell ± depleted mice showed a strong but reduced expression of murine IL -12. Expression of DNA encoding human instead of murine IL -12 resulted in a significantly lower and transient expression, indicating that not plasmid -derived IL -12 production alone but the immune system of the host contributes to the long -lasting antimetastatic effect. It may be attributable to an autocrine feedback mechanism maintaining murine IL -12 expression, whereby several cell populations including NK cells are involved. Cancer Gene Therapy ( 2000 ) 7, 1557 ± 1565

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“…The human GM-CSF pDNA was included in the vaccine to increase the immunogenicity as GM-CSF is known to attract dendritic cells to the site of administration and enhance the maturation of dendritic cell precursors which play an important role in antigen presentation. [19][20][21][22][23][24] While co-administration of GM-CSF pDNA has been demonstrated to enhance the immunogenicity of pDNA vaccines, [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] the overexpression of GM-CSF in transgenic mice has been demonstrated to result in adverse pathology associated with overaccumulation of macrophages in tissues, accumulation of macrophages in the peritoneal and pleural cavities, retinal damage, muscle wasting, and a fatal tissue damage syndrome. 37 Thus, the inclusion of GM-CSF in the vaccine raised several important theoretical safety concerns which had to be addressed before the vaccine could be taken into a clinical trial with healthy volunteers.…”

Section: Discussionmentioning

confidence: 99%

Safety of a GM-CSF adjuvant-plasmid DNA malaria vaccine

Monteith

Horton

et al. 2001

Gene Ther

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MuStDO 5 is a multivalent plasmid DNA vaccine for malaria comprised of five plasmid DNAs encoding five proteins from Plasmodium falciparum and one plasmid DNA encoding human GM-CSF. To evaluate the safety of MuStDO 5, a series of pre-clinical studies were conducted in mice and rabbits. In pharmacology studies in mice, GM-CSF could not be detected in the serum following either intramuscular or a combined intramuscular/intradermal administration of the vaccine, but was readily detected in the muscle following

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Enhanced protection against viral infection by co-administration of plasmid DNA coding for viral antigen and cytokines in mice

Cited by 37 publications

References 43 publications

DNA Vaccination against La Crosse Virus

DNA Vaccination against La Crosse Virus

Induction of long-lasting cytokine effect by injection of IL-12 encoding plasmid DNA

Safety of a GM-CSF adjuvant-plasmid DNA malaria vaccine

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