DNA vaccines: Successes and limitations in cancer and infectious disease

Lowe, Devin B.; Shearer, Michael H.; Kennedy, Ronald C.

doi:10.1002/jcb.20775

Cited by 37 publications

(28 citation statements)

References 59 publications

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“…27 DNA vaccines allow us to express antigens in vivo in such a way that both humoral and cell-mediated immune responses can be evoked simultaneously. DNA vaccines also do not bear the safety risks associated with live vaccines.…”

Section: Mif/ttx Dna Vaccination and Sepsis S Tohyama Et Almentioning

confidence: 99%

A novel DNA vaccine-targeting macrophage migration inhibitory factor improves the survival of mice with sepsis

et al. 2008

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Sepsis is a common and frequently fatal condition and there is an urgent need for new therapies that will further reduce sepsis-induced mortality. Macrophage migration inhibitory (MIF) factor is important in the regulation of innate and adaptive immunity and is believed to play a key regulatory role in sepsis and autoimmune disease. As MIF deficiency or immunoneutralization protects mice or rats from fatal endotoxic shock or other inflammatory diseases, we examined whether DNA vaccination against this molecule would also be protective. DNA vaccines can stimulate both humoral and cellular immunity simultaneously and have been shown to be effective against a variety of pathogens or cytokinedriven pathologies. Mice were immunized with a MIF/tetanus toxin (TTX) DNA vaccine and sepsis was then induced by lipopolysaccharide or cecal ligation and puncture. The MIF/ TTX DNA-vaccinated mice were protected from the lethal effect of sepsis compared with control-vaccinated mice in both models. Compared with the control-vaccinated mice, the MIF/TTX DNA-vaccinated mice also showed significantly lower serum tumor necrosis factor (TNF)-a protein levels and reduced mRNA expression of TNF-a, interleukin (IL)-1b, IL-6, macrophage inflammatory protein-2 and Toll-like receptor-4 in the lungs. Thus, the MIF/TTX DNA vaccine may be useful for the prophylaxis of septic shock.

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Section: Mif/ttx Dna Vaccination and Sepsis S Tohyama Et Almentioning

confidence: 99%

A novel DNA vaccine-targeting macrophage migration inhibitory factor improves the survival of mice with sepsis

et al. 2008

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“…DIVA diagnostics hampering, selection and use of adjuvants, requirements for multiple injections), and only produce a short-lived humoral immune response. Vaccination with plasmid DNA is an active area of investigation that is being applied to cancer and microbial pathogens associated with infectious diseases (Lowe et al, 2006). DNA vaccines have been reported to persist in muscle for over one year, they induce effective immune responses with bacterial antigens, and are simply produced (Wolff et al, 1992;Gurunathan et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Nucleic acid immunization has been reported to induce both humoral and cellular immunity in many infectious disease models (Lowe et al, 2006). Plasmids pcDNA3.1/P48, pVAX1/P48, and pCMV-Script/P48 were constructed in order to investigate the potential of a plasmid carrying the 48 kDa antigen gene of M. agalactiae in eliciting immune responses.…”

Section: Construction and Expression Of Plasmid Carrying P48 Genementioning

confidence: 99%

Genetic immunization with the immunodominant antigen P48 of Mycoplasma agalactiae stimulates a mixed adaptive immune response in BALBc mice

Chessa

Pittau

Puricelli

et al. 2009

Research in Veterinary Science

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a b s t r a c tA DNA vaccine against contagious agalactia was developed for the first time, encoding the P48 of Mycoplasma agalactiae. Specific immune responses elicited in BALB/c mice were evaluated. Both total IgG and IgG1 were detected in mice vaccinated with pVAX1/P48. Proliferation of mononuclear cells of the spleen, levels of gamma interferon, interleukin-12, and interleukin-2 mRNAs were enhanced in immunized animals. Results indicate that pVAX1/P48 vaccination induced both T h 1 and T h 2 immune responses. Nucleic acid immunization could be a new strategy against M. agalactiae infections and may be potentially used to develop vaccines for other Mycoplasma diseases.

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“…The mice were treated with OSU-HDAC42 1 day after DNA vaccination. Tumor size was determine using a caliper at 3 day intervals and calculated using the formula for a rational ellipse: (m 1 2 Â m 2 Â 0.5236), where m 1 represents the short axis and m 2 the longer axis. Mice were killed when the mean diameter of the tumor exceeded 2000 mm 3 or the mouse was in poor condition and expected shortly to become moribund.…”

Section: Detection Of Green Fluorescent Protein (Gfp)-positive Dendrimentioning

confidence: 99%

An HDAC inhibitor enhances the antitumor activity of a CMV promoter-driven DNA vaccine

Lai

et al. 2009

Cancer Gene Ther

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The cytomegalovirus (CMV) promoter is considered to be one of the strongest promoters for driving the in vivo expression of genes encoded by DNA vaccines. However, the efficacy of DNA vaccines has so far been disappointing (particularly in humans), and this might be explained in part by histone deacetylase (HDAC)-mediated chromatin condensation. Hence, we sought to investigate whether increasing the expression of DNA vaccine antigens with the HDAC inhibitor OSU-HDAC42 would enhance the efficacy of DNA vaccines in vivo. A luciferase assay was used to determine the effects of OSU-HDAC42 on CMV promoter-driven DNA plasmids in vitro and in vivo. Three HDAC inhibitors were able to activate expression from the CMV promoter in NIH3T3 cells and MBT-2 bladder cancer cells. The expression of luciferase was significantly enhanced by co-administration of pCMV-luciferase and OSU-HDAC42 in mice. To explore whether OSU-HDAC42 could enhance the specific antitumor activity of a neu DNA vaccine driven by the CMV promoter, we evaluated therapeutic effects and immune responses in a mouse tumor natively overexpressing HER2/neu. Mice receiving OSU-HDAC42 in combination with the CMV-promoter neu DNA vaccine exhibited stronger antitumor effects than mice given the DNA vaccine only. In addition, a correlation between the antitumor effects and the specific cellular immune responses was observed in the mice receiving the DNA vaccine and OSU-HDAC42.

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DNA vaccines: Successes and limitations in cancer and infectious disease

Cited by 37 publications

References 59 publications

A novel DNA vaccine-targeting macrophage migration inhibitory factor improves the survival of mice with sepsis

A novel DNA vaccine-targeting macrophage migration inhibitory factor improves the survival of mice with sepsis

Genetic immunization with the immunodominant antigen P48 of Mycoplasma agalactiae stimulates a mixed adaptive immune response in BALBc mice

An HDAC inhibitor enhances the antitumor activity of a CMV promoter-driven DNA vaccine

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