July 31 2010
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Aldevron licenses HyperGRO™ DNA manufacturing technology from Nature Technology Corporation.
Fargo, ND (July 27, 2010) Aldevron, a biotechnology company, has licensed the HyperGRO™ DNA production processes from Nature Technology Corporation (NTC) for use in Aldevron’s clinical manufacturing programs.

According to Michael Chambers, President and CEO of Aldevron, “We are very excited to have access to Nature’s HyperGRO™ technology. By working together, Aldevron and NTC can provide our clients’ with better options for clinical-grade manufacturing.“ NTC’s HyperGRO™ processes will be combined with Aldevron’s downstream purification technology to manufacture DNA vaccine and gene therapy products. The result will be a very high-yielding DNA production process that will allow Aldevron to manufacture larger amounts of DNA for an increased number of applications.

After collaborating with NTC for several years, our testing and evaluation indicates that NTC’s HyperGRO™ plasmid purification processes provide some of the best yields and highest purity for many applications while also maintaining the fidelity and integrity of the plasmid. This will address client requirements for dramatically increased product yield and purity at a very competitive cost.
Immunologic Response to Xenogeneic gp100 DNA in Melanoma Patients
Immunologic Response to Xenogeneic gp100 DNA in Melanoma Patients: Comparison of Particle-Mediated Epidermal Delivery with Intramuscular Injection.

Purpose: Prior studies show that i.m. injection of xenogeneic orthologues of melanosomal antigens (tyrosinase, gp100) induces CD8+ T-cell responses to the syngeneic protein. To further define the optimal vaccination strategy, we conducted a pilot clinical trial comparing i.m. injection with particle-mediated epidermal delivery (PMED).
Application of Electroporation in DNA Vaccination Protocols.
Vaccination is historically one of the most important methods for preventing infectious diseases in humans and animals. Due to recent advances in understanding the biology of the immune system, a more rational design of vaccines and vaccination strategies such as those based on gene transfer has been proposed. In particular, naked DNA vaccination is emerging as a promising approach for introducing foreign antigens into the host, inducing protective immunity against infectious diseases and malignant tumours. Plasmid DNA vaccines offer several advantages in comparison to traditional vaccines such as safety, tolerability and feasibility in manufacture. Nevertheless, because of their poor immunogenicity, plasmid DNA vaccines need further implementation. Recent data suggest electroporation as a useful strategy to improve DNA-based vaccination protocols, being able to stimulate both the humoural and cellular immune responses. In preclinical trials, electroporation is successfully used in prime-boost combination protocols and its efficacy and tolerability have been demonstrated in Phase I clinical trials. Since these initial results appear promising, in the next future we will assist further developments of naked DNA vaccination associated to the electroporation technology. This approach not only provides the basis for human studies but also a practical application to veterinary medicine.

Source: Current Gene Therapy, Volume 10, Number 4, August 2010 , pp. 281-286(6).


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Immunogenicity and Persistence of a Targeted Anti-caries DNA Vaccine.
We have previously reported that a targeted anti-caries DNA vaccine, pGJA-P, induced accelerated and increased antibody responses compared with a non-targeted anti-caries DNA vaccine. Recently, pGJA-P/VAX, a new targeted anti-caries DNA vaccine for human trials, was constructed by replacing the pCI vector used in the construction of pGJA-P with pVAX1, the only vector authorized by the US Food and Drug Administration in clinical trials. Here, we report on our exploration of the kinetics of the antibody responses generated following pGJA-P/VAX immunization and the persistence of pGJA-P/VAX at both the inoculation site and the draining lymph nodes. Intranasal vaccination of mice with pGJA-P/VAX induced strong antibody responses that lasted for more than 6 months. Furthermore, pGJA-P/VAX could still be detected at both the inoculation site and the draining cervical lymph nodes 6 months after immunization. Thus, the persistent immune responses are likely due to the DNA depot in the host, which acts as a booster immunization.


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Immunacia’s Genetic Immunity Reports Phase II Data on DermaVir,
Immunacia’s Genetic Immunity Reports Phase II Data on DermaVir, a Therapeutic Vaccine for HIV/AIDS, During the XVIII International AIDS Conference: A 70% Viral Load Reduction Demonstrated in HIV Drug-naïve Individuals

BUDAPEST, Hungary & MCLEAN, Va.--(BUSINESS WIRE)--Genetic Immunity, a US/Hungarian biopharmaceutical company developing nanomedicine-based immunotherapies for HIV/AIDS and other chronic diseases, is releasing Phase II data on the Company’s novel DermaVir therapeutic vaccine for HIV/AIDS during the XVIII International AIDS Conference this week in Vienna, Austria. DermaVir, the first dendritic cell-targeting topical HIV vaccine candidate, employs nanotechnology to induce multi-faceted and long-lived immune responses capable of eliminating HIV infected cells.
DNA vaccine constructs expressing Mycobacterium tuberculosis-specific genes induce immune responses.
RD1 PE35, PPE68, EsxA, EsxB and RD9 EsxV genes are present in Mycobacterium tuberculosis genome but deleted in M. bovis BCG. The aim of this study was to clone these genes into DNA vaccine vectors capable of expressing them in eukaryotic cells as fusion proteins, fused with immunostimulatory signal peptides of human interleukin-2 (hIL-2) and tissue plasminogen activator (tPA), and evaluate the recombinant DNA vaccine constructs for induction of antigen specific cellular immune responses in mice. DNA corresponding to the above RD1 and RD9 genes were cloned into DNA vaccine plasmid vectors pUMVC6 and pUMVC7 (with hIL-2 and tPA signal peptides, respectively), and a total of 10 recombinant DNA vaccine constructs were obtained. BALB/c mice were immunized with the parent and recombinant plasmids and their spleen cells were tested for antigen-induced proliferation with antigens of M. tuberculosis and pure proteins corresponding to the cloned genes. The results showed that antigen-specific proliferation responses were observed for a given antigen only with spleen cells of mice immunized with the homologous recombinant DNA vaccine construct. The mice immunized with the parent plasmids did not show positive immune responses to any of the antigens of the cloned genes. The ability of the DNA vaccine constructs to elicit cellular immune responses makes them an attractive weapon as a safer vaccine candidate for preventive and therapeutic applications against TB.


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Ichor Medical Systems Awarded Contract to Further Development of Vaccine for Biodefense Pathogen.
San Diego, CA -- Ichor Medical Systems (Ichor) of San Diego announced today that they have received a $2.2 million contract from the US Defense Threat Reduction Agency (DTRA). The contract will fund Phase I human clinical testing of a promising DNA vaccine candidate for Venezuelan Equine Encephalitis Virus (VEEV) delivered using Ichor’s TriGridTM electroporation system.

The development of medical countermeasures for biodefense agents and emerging pathogens has been identified as a priority by DTRA and related government agencies. The VEEV pathogen is listed as a Category B agent by the Centers for Disease Control (CDC) and is considered an important biodefense risk in part due to its stability when aerosolized as well as its ability to rapidly incapacitate infected individuals.
In collaboration with researchers at the US Army Medical Research Institute of Infectious Diseases (USAMRIID) and with funding from another DTRA contract, Ichor has identified a DNA-based vaccine candidate for VEEV. When delivered by TriGridTM electroporation, the vaccine candidate demonstrated compelling safety and efficacy characteristics in nonhuman primates, including rapid induction of virus-neutralizing antibody responses that conferred protection from viral challenge.

“The Ichor/USAMRIID program is aligned with DTRA’s mission of developing biological countermeasures and will address a specific unmet medical need for a safe and effective VEEV vaccine,” stated Dr. Connie Schmaljohn, Senior Research Scientist at USAMRIID.
Bob Bernard, Ichor CEO, said, “We are pleased to continue our collaboration with USAMRIID in developing this and other biodefense vaccines. We anticipate the resulting human data will position the TriGridTM as a vaccine delivery platform for use in a number of biodefense applications as well as other infectious disease indications.”


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Vector Choice Determines Immunogenicity and Potency of Genetic Vaccines Against Angola Marburgvirus in Nonhuman Primates.
The immunogenicity and durability of genetic vaccines is influenced by the composition of gene inserts and choice of delivery vector. DNA vectors are a promising vaccine approach showing efficacy when combined in prime-boost regimens with recombinant protein or viral vectors, but they have shown limited comparative efficacy as a stand-alone platform in primates, due possibly to suboptimal gene expression or cell targeting. Here, regimens using DNA plasmids modified for optimal antigen expression and rAd vectors, all encoding the glycoprotein (GP) gene from Marburg virus (MARV) Angola were compared for their ability to provide immune protection against lethal MARV Angola infection. Heterologous DNA-GP/rAd5-GP prime-boost and single modality rAd5-GP, as well as the DNA-GP only vaccine prevented death in all vaccinated subjects after challenge with a lethal dose of MARV Angola. The DNA/DNA vaccine induced humoral responses comparable to a single inoculation with rAd5-GP, as well as CD4+ and CD8+ cellular immune responses, with skewing toward CD4+ T-cell activity against MARV GP. Vaccine regimens containing rAd-GP, alone or as a boost, exhibited cellular responses with CD8+ T cell dominance. Across vaccine groups, CD8+ T-cell subset dominance comprising cells exhibiting a TNF-{alpha} and IFN-{gamma} double-positive functional phenotype was associated with an absence or low frequency of clinical symptoms, suggesting that both the magnitude and functional phenotype of CD8+ T-cells may determine vaccine efficacy against infection by MARV Angola.


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Changes of cytokines and IgG antibody in chickens vaccinated with DNA vaccines encoding Eimeria acervulina lactate dehydrogenase.
The aim of this study was to investigate the changes of cytokines and specific serum IgG in chickens following vaccination with DNA vaccines encoding either Eimeria acervulina (E. acervulina) lactate dehydrogenase (LDH) antigen or LDH and chicken IL-2 or IFN-gamma. Two-week-old chickens were randomly divided into five groups. Experimental group of chickens were immunized with DNA vaccines while control group of chickens were injected with pVAX1 plasmid alone or sterile water. All immunizations were boosted 2 weeks later. The LDH-specific IgG antibody response was measured at weeks 1-6 post-second immunization. The result showed that the antibody titers in chickens vaccinated with DNA vaccines were significantly different from those of the control groups 1 week after the second immunization (P<0.05) and reached the maximum values 3 weeks post-second immunization. The systemic and local cytokine mRNA expression was determined by quantitative RT-PCR 7 days post-second immunization. The specific IgG antibody levels against LDH of all chickens vaccinated with vaccines were increased compared to those of sterile water (H(2)O) and plasmid (pVAX1) control chickens 1-6 weeks post-second immunization (P<0.05). The mRNA levels of IFN-gamma, IL-2, TNFSF15, IL-17D as well as TGF-beta4 in both spleen and cecal tonsil were also increased in experimental chickens. In contrast, the only significant change of IL-4 mRNA level was observed in spleen of chickens immunized with pVAX-LDH-IL-2 compared with pVAX-LDH and control groups (P<0.05). These results suggested that DNA vaccines could increase the IgG antibody level and induce the expressions of cytokines.


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Vaccine-induced IgG2 anti-HIV p24 is associated with control of HIV in patients with a 'high-affinity' Fc[gamma]RIIa genotype.
Objectives: We have previously shown that vaccination with a recombinant fowlpox virus carrying the genes for HIV Gag-Pol and interferon-gamma (IFN-[gamma]) was associated with partial control of HIV replication after antiretroviral therapy (ART) was ceased but not with increased anti-HIV T-cell responses. Because IFN-[gamma] enhances IgG2 production, and IgG2 antibodies to HIV antigens and the 'high-affinity' polymorphism of Fc[gamma]RIIa (the major Fc receptor for IgG2) have been associated with a favourable outcome of HIV infection, we examined the association of IgG2 antibodies to HIV p24 and 'high-affinity' polymorphisms of Fc[gamma]RIIa with control of HIV replication in these patients.


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Commensal/ Food bacteria-based DNA vaccine and DNA vaccine-delivery system.
The present invention is a medical invention related to a new HIV (Human Immunodeficiency Virus – the causative agent for AIDS) vaccine-delivery system. A majority of the HIV infections occur at mucosal sites either by sexual contact or by breastfeeding. Therefore, blocking HIV entry at the mucosal site is critical to prevent infection. Various bacterial vectors are used to deliver HIV vaccines, including Listeria, Salmonella, Shigella, and Yersinia. However, they are unsuitable because these potential lethal pathogens require extensive attenuations rendering them less effective. Secondly, none of these bacteria colonize the human oral cavity or the vagina, the ports of HIV entry. The present inventors have constructed novel HIV DNA mucosal vaccines based on commensal (Streptococcus gordonii) and food (Lactococcus lactis) bacteria. These bacteria will release DNA vaccine plasmids inside the host immune cells in the orogastrointestinal and vaginal tracts, and may induce strong immune responses in animals. The system of the present invention can deliver live vaccines safely as a food. It can deliver many types of DNA vaccines to the mucosal surfaces for disease prevention and/or treatment.



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Conference listing
· The Immunotherapeutics & Vaccines Summit
Cambridge MA-USA
17-19 Aug 2010

· BioProcess International Conference
Providence RI-USA
20-24 Sep 2010

· Malaria Vaccines for the World
Washington DC-USA
28-30 Sep 2010

· 4th Vaccine and ISV Global Congress
Vienna Austria
3-5 Oct 2010

· World Vaccine Congress LYON
Lyon France
4-7 Oct 2010

· Modern Vaccines/Adjuvants Formulation
Cannes France
13-15 Oct 2010

· Next Generation Vaccines
Vienna Austria
21-22 Oct 2010

· Gene-Based Vaccines
Cannes France
8-10 Nov 2010

· Influenza Congress USA 2010
Washington DC-USA
08-10 Nov 2010

· Vaccines All Things Considered
Washington DC-USA
08-09 Nov 2010

· Modern Veterinary Vaccines & Adjuvants
Budapest Hungary
17-19 Nov 2010

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