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Reports summarize DNA vaccines study results from L.R. Smith |
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 Researchers detail in 'Phase 1 clinical trials of the safety and immunogenicity of adjuvanted plasmid DNA vaccines encoding influenza A virus H5 hemagglutinin,' new data in dna. "Development of vaccines against highly pathogenic avian influenza virus H5N1 subtypes posing a pandemic threat remains a priority. Limitations in manufacturing capacity and production time of conventional inactivated vaccines highlight the need for additional approaches," scientists in the United States report.
"We conducted two double-blind, placebo-controlled phase 1 studies involving a total of 103 healthy adults who received two intramuscular injections of Vaxfectin-adjuvanted plasmid DNA...
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piggyBac transposon to create HIV-1 gag transgenic insect cell lines |
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Use of the piggyBac transposon to create HIV-1 gag transgenic insect cell lines for continuous VLP production.
Insect baculovirus-produced Human immunodeficiency virus type 1 (HIV-1) Gag virus-like-particles (VLPs) stimulate good humoral and cell-mediated immune responses in animals and are thought to be suitable as a vaccine candidate. Drawbacks to this production system include contamination of VLP preparations with baculovirus and the necessity for routine maintenance of infectious baculovirus stock. We used piggyBac transposition as a novel method to create transgenic insect cell lines for continuous VLP production as an alternative to the baculovirus system. RESULTS: Transgenic cell lines maintained stable gag transgene integration and expression up to 100 cell passages, and although the level of VLPs produced was low compared to baculovirus-produced VLPs, they appeared similar in size and morphology to baculovirus-expressed VLPs. In a murine immunogenicity study, whereas baculovirus-produced VLPs elicited good CD4 immune responses in mice when used to boost a prime with a DNA vaccine, no boost response was elicited by transgenically produced VLPs. CONCLUSION: Transgenic insect cells are stable and can produce HIV Pr55 Gag VLPs for over 100 passages: this novel result may simplify strategies aimed at making protein subunit vaccines for HIV. Immunogenicity of the Gag VLPs in mice was less than that of baculovirus-produced VLPs, which may be due to lack of baculovirus glycoprotein incorporation in the transgenic cell VLPs. Improved yield and immunogenicity of transgenic cell-produced VLPs may be achieved with the addition of further genetic elements into the piggyBac integron.
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Administration of vitamin D3 improves antimetastatic efficacy of cancer vaccine therapy |
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Administration of vitamin D3 improves antimetastatic efficacy of cancer vaccine therapy of Lewis lung carcinoma.
To analyze antitumor efficacy of experimental cancer vaccine therapy combined with introduction of vitamin D3 (VD3) for treatment of Lewis lung carcinoma (3LL). Materials and Methods: Cancer vaccines composed from recombinant murine beta-defensin-2 (mBD-2) and 3LL cell lysate, or DNA, coding for mBD-2-Muc1 fusion construct cloned in pcDNA3+ vector, were prepared and used for intradermal vaccination. Experimental cancer vaccines introduced i. d. at therapeutic and prophylactic regimens to 3LLbearing C57Bl mice, were applied alone or in combination with VD3 (administered per os) and/or low-dose cyclophosphamide (CP, administered intraperitoneal). Efficacy of treatments was analyzed by primary tumor growth dynamics indexes and by metastasis rate in vaccinated animals. Results: As it has been shown, administration of the protein-based vaccine composed from mBD-2 and 3LL cell lysate in combination with VD3 and CP, but not in VD3 free setting, led to significant suppression of primary tumor growth (p < 0.005) and had significant antimetastatic effect. Introduction of VD3 with or without CP in the scheme of treatment with mBD-2-Muc1-DNA vaccine at therapeutic regimen has led to significant suppression of primary tumor (p < 0.05) and metastasis volumes (p < 0.005), while in the groups of animals treated with DNA-vaccine + VD3 with or without CP at prophylactic regimen, significant antimetastatic effect (p < 0.05) and elevation of average life-span (p < 0.05) have been registered. Conclusion: The results of this pilot study have shown promising clinical effects of VD3 administration in combination with cancer vaccinotherapy in vivo.
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gene-based vaccination against H5N1 influenza in mouse and ferret |
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Comparative efficacy of hemagglutinin, nucleoprotein, and matrix 2 protein gene-based vaccination against H5N1 influenza in mouse and ferret.
Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products. The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes. Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus. In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA. However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased. To explore this question in a model relevant to human disease, ferrets were immunized with DNA/rAd5 vaccines encoding NP, M2, HA, NP+M2 or HA+NP+M2. Only HA or HA+NP+M2 vaccination conferred protection against a stringent virus challenge. Therefore, while gene-based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets. These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge.
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Immunocontraceptive Effect of DNA Vaccine Targeting Fertilin-Beta |
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In previous study, two eukaryotic expression plasmids pSG.SS.YL and pSG.SS.C3d3.YL were successfully constructed and transfected in HEK293 cells. Now, we want to evaluate the immunocontraceptive effect of these two DNA vaccines that target the extracellular domain of sperm antigen fertilin β subunit in Kunming male mice. Method of studyq94;
DNA vaccines pSG.SS.YL and pSG.SS.C3d3.YL were injected into Kunming male mice three times at 0, 4, and 8r01;weeks, respectively. An antifertility effect was observed. Serum antibody and cytokines were also detected. Resultsq94;
Both vaccines significantly decreased both the pregnancy rate and the number of newborns. The serum levels of IL-2 and INF significantly decreased, whereas the levels of IL-4 and IL-10 significantly increased.
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GP96 C-terminal improves Her2/neu DNA vaccine. |
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DNA vaccines ensure protective immunity against tumors in a variety of experimental models. The favorite target tumor-associated antigens have been those that are frequently expressed by human tumors, such as Her2. However, the efficacy of active vaccination is limited because Her2 is a self-tolerated antigen. Many strategies have been applied to increase the efficacy of DNA vaccination, such as fusion or co-administration of Her2 with cytokine and co-stimulatory molecules. GP96 is involved in innate and adaptive immune responses and evokes potent activation and maturation of dendritic cells along with increased secretion of pro-inflammatory cytokines. On the basis of previous studies, we expected the C-terminal of GP96 to act as a package and as a suitable substitute for both cytokine and co-stimulatory genes.
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Effect of Different Disaccharides on Stability after Lyophilisation |
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Naked Plasmid DNA Formulation: Effect of Different Disaccharides on Stability after Lyophilisation.
Since plasmid DNA (pDNA) is unstable in solution, lyophilisation can be used to increase product shelf life. To prevent stress on pDNA molecules during lyophilisation, cryo- and lyoprotectants have to be added to the formulation. This study assessed the effect of disaccharides on naked pDNA stability after lyophilisation using accelerated stability studies. Naked pDNA was lyophilised with sucrose, trehalose, maltose or lactose in an excipient/DNA w/w ratio of 20. To one part of the vials extra residual moisture was introduced by placing the vials half opened in a 25 degrees C/60% RH climate chamber, before placing all vials in climate chambers (25 degrees C/60% RH and 40 degrees C/75% RH) for stability studies. An ex vivo human skin model was used to assess the effect of disaccharides on transfection efficiency. Lyophilisation resulted in amorphous cakes for all disaccharides with a residual water content of 0.8% w/w. Storage at 40 degrees C/75% RH resulted in decreasing supercoiled (SC) purity levels (sucrose and trehalose maintained approximately 80% SC purity), but not in physical collapse.
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Immunogenicity and protective efficacy of mycobacterial DNA vaccines |
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DNA-based vaccines, alone or in combination with other sub-unit vaccination regimes, represent an alternative to live mycobacterial vaccines for protective immunization against tuberculosis. Here, we have used a murine immunization or Mycobacteriam bovis aerosol challenge model to assess the immunogenicity and protective efficacy of mycobacterial DNA vaccines. Mice that received immunization with DNA constructs encoding M. bovis antigen 85A (Ag85–A) and arget(ESAT-6) produced measurable interferon-gamma (IFN-γ) responses to CD4+ T-cell epitope-peptide recall antigens in vitro. The magnitude of these responses was enhanced by co-delivery of a construct encoding murine cytokines (macrophage inhibitory protein (MIP)-1α or interleukin(IL)-7), although they did not the match responses observed in mice that received Bacille Calmettew22;Guerin(BCG) immunisation.
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Protection against the allergic airway inflammation |
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Protection against the allergic airway inflammation depends on the modulation of spleen dendritic cell function and induction of regulatory T cells in mice.
Background: Allergen-induced imbalance of specific T regulatory (Treg) cells and T helper 2 cells plays a decisive role in the development of immune response against allergens.
Objective: To evaluate effects and potential mechanisms of DNA vaccine containing ovalbumin (OVA) and Fc fusion on allergic airway inflammation.
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Vical Secures Funding to Proceed With Phase 1 Trial of H1N1 |
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SAN DIEGO, March 22, 2010 (GLOBE NEWSWIRE) -- Vical Incorporated (Nasdaq:VICL) announced today that the U.S. Navy, through the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., has awarded Vical a contract to conduct a Phase 1 clinical trial of the company's Vaxfectin®-formulated DNA vaccine against A/H1N1 pandemic influenza (swine flu). Vical had previously been awarded a contract by the U.S. Navy, in collaboration with the Transformational Medical Technologies Initiative (TMTI) of the Department of Defense (DoD), to support large-scale cGMP vaccine manufacturing and related clinical and regulatory preparations for the trial, bringing total U.S. government funding for this project to approximately $2 million.
The Investigational New Drug (IND) application describing the trial design had been allowed by the U.S. Food and Drug Administration (FDA) in 2009, so the new funding clears the path for the trial to begin.
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Advances in Chikungunya Virus DNA Vaccine |
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A leader in vaccine design, development, and distribution, Inovio Biomedical Corporation, informed that its SynCon™ Chikungunya virus DNA vaccine generated protective neutralizing antibody responses in a monkey model.
The Chikungunya virus is a new alpha virus carried by mosquitoes that originated in tropical Africa and Asia. It has been known to have an infection rate of up to 45%. Although not life threatening, this virus causes acute human morbidity, presenting serious fever and weakening joint pain, and it could take over a year to cure.
It has been discovered that different mosquitoes normally found in developed countries, including Europe and the United States, can transmit the Chikungunya virus, making it a threat for people in other geographies outside its territories of origin. The virus is already prevalent in several world regions and clearly has epidemic potential.
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