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Frederick, MD, United States

Pushko P.,Medigen, Inc. | Pumpens P.,Latvian Biomedical Research and Study Center | Pumpens P.,University of Latvia | Grens E.,Latvian Biomedical Research and Study Center
Intervirology | Year: 2013

Virus-like particle (VLP) technology is a promising approach for the construction of novel vaccines, diagnostic tools, and gene therapy vectors. Initially, VLPs were primarily derived from non-enveloped icosahedral or helical viruses and proved to be viable vaccine candidates due to their effective presentation of epitopes in a native conformation. VLP technology has also been used to prepare chimeric VLPs decorated with genetically fused or chemically coupled epitope stretches selected from immunologically defined target proteins. However, structural constraints associated with the rigid geometrical architecture of icosahedral or helical VLPs pose challenges for the expression and presentation of large epitopes. Complex VLPs derived from non-symmetric enveloped viruses are increasingly being used to incorporate large epitopes and even full-length foreign proteins. Pleomorphic VLPs derived from influenza or other enveloped viruses can accommodate multiple full-length and/or chimeric proteins that can be rationally designed for multifunctional purposes, including multivalent vaccines. Therefore, a second generation of VLP carriers is represented by complex particles reconstructed from natural or chimeric structural proteins derived from complex enveloped viruses. Further development of safe and efficient VLP nanotechnology may require a rational combination of both approaches. Copyright © 2013 S. Karger AG, Basel. Source


Patent
Medigen, Inc. | Date: 2011-01-03

Described herein are i-DNA vectors and vaccines and methods for using the same. The i-DNA generates live attenuated vaccines in eukaryotic cells in vitro or in vivo for pathogenic RNA viruses, particularly chikungunya virus (CHIKV). When iDNA is injected into the vaccine recipient, RNA of live attenuated virus is generated by in vivo transcription in the recipients tissues. This initiates production of progeny attenuated viruses in the tissues of the vaccine recipient, as well as elicitation of an effective immune response protecting against wild-type, non-attenuated virus.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 117.99K | Year: 2011

DESCRIPTION (provided by applicant): Live attenuated vaccine 17D has been used since the 1950s for vaccination against yellow fever (YF) with a remarkable record of safety and efficacy. More than 500 million people have been vaccinated, and the World Health Organization (WHO) strongly recommends to continue vaccinations in at-risk countries. The weaknesses of the vaccine include outdated manufacturing and the need of a cold chain , which accounts for up to 80% of cost in endemic areas. In rare cases, 17D vaccine causes adverse effects including allergies, neurologic disorders, and viscerotropic disease. The vaccine represents a population of genetically distinct viruses, some of which may be responsible for adverse reactions. The main goal of this revised Phase I SBIR is the production and evaluation of a conceptually novel YF vaccine. We propose a novel technology of infectious DNA (i-DNA) as YF vaccine. A unique feature of this technology is that the full-length copy of 17D genome is placed in the i-DNAplasmid in the context of optimized eukaryotic promoter and regulatory sequences. Thus, live attenuated 17D virus can be launched in vivo directly from the i-DNA plasmid. Since the 17D i-DNA represents a molecular clone, it will generate a uniform population of 17D virus thus potentially improving safety. We will also prepare two i-DNA variants by de-optimization of translational codons within C-prM-E genes with the view to improve vaccine safety and genetic stability. Experimental YF i-DNA vaccines will be evaluated in vitro and in vivo along with the current 17D vaccine. Immunogenicity and safety profiles including neurotropic and viscerotropic adverse effects will be evaluated in the recently developed models of immunosupressed hamster and A129 knockout mouse. Thus, characteristics of candidate i-DNA vaccines will be evaluated in the two preclinical models with immunocompromised background, which mimicks frequent situation in the endemic areas and will provide accurate determination of safety and immunogenicity profiles of the vaccines. In summary, i-DNA vaccination combines the simplicity of DNA vaccines with the exceptional efficacy of live attenuated vaccines. The i-DNA can potentially improve safety, does not require cold chain and is easy to manufacture and scale-up in emergency scenarios. Further, bacterially generated i-DNA will contain CpG motifs, which are expected to activate innate immune responses and improve immunogenicity. If successful, this technology may represent a revolutionary improvement of YF vaccine and vaccination practice against yellow fever. PUBLIC HEALTH RELEVANCE: Yellow fever (YF) is a re-emerging pathogen and a public health problem worldwide. The focus of this Phase I SBIR study is the production and evaluation of a conceptually novel vaccine for YF. We hypothesize that safety and immunogenicity of live attenuated 17D vaccine can be improved by using the infectious DNA (i-DNA) technology. This will result in a unique YF vaccine, which will combine the simplicity of DNAvaccines with the exceptional efficacy of live attenuated vaccine.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.48M | Year: 2011

This Phase II, SBIR contract is for the advanced vaccine efficacy studies, which involve TRAMP tumor challenge of vaccinated PSA+ transgenic mice. Engineered for increased immunogenicity PSA variants will be delivered and expressed in PSA+ mice using novelvector VLP (vVLP_ vaccine platform. The latter represent non-replicating virus-like particles configured to encapsidate expression vector for in vivo delivery and expression of engineered PSA genes.


Patent
Medigen, Inc. | Date: 2015-07-02

Described herein are i-DNA vectors and vaccines and methods for using the same. The i-DNA generates live attenuated vaccines in eukaryotic cells in vitro or in vivo for pathogenic RNA viruses, particularly chikungunya virus (CHIKV). When iDNA is injected into the vaccine recipient, RNA of live attenuated virus is generated by in vivo transcription in the recipients tissues. This initiates production of progeny attenuated viruses in the tissues of the vaccine recipient, as well as elicitation of an effective immune response protecting against wild-type, non-attenuated virus.

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