scholarly journals Vaccinia virus vectors: new strategies for producing recombinant vaccines.

1990 ◽  
Vol 3 (2) ◽  
pp. 153-170 ◽  
Author(s):  
D E Hruby

The development and continued refinement of techniques for the efficient insertion and expression of heterologous DNA sequences from within the genomic context of infectious vaccinia virus recombinants are among the most promising current approaches towards effective immunoprophylaxis against a variety of protozoan, viral, and bacterial human pathogens. Because of its medical relevance, this area is the subject of intense research interest and has evolved rapidly during the past several years. This review (i) provides an updated overview of the technology that exists for assembling recombinant vaccinia virus strains, (ii) discusses the advantages and disadvantages of these approaches, (iii) outlines the areas of outgoing research directed towards overcoming the limitations of current techniques, and (iv) provides some insight (i.e., speculation) about probable future refinements in the use of vaccinia virus as a vector.

Author(s):  
S. Shchelkunov ◽  
A. Sergeev ◽  
A. Kabanov ◽  
S. Yakubitskyi ◽  
T. Bauer ◽  
...  

Vaccinia virus had played a key role in the global smallpox eradication. However, in case of mass vaccination with various vaccinia virus strains severe side effects were revealed sometimes ending up with lethal outcomes, especially in immunocompromised humans. Hence, the World Health Organization recommended to cancel smallpox vaccination after declaring in 1980 about smallpox eradication. Over last 40 years, human population virtually lost immunity not only against smallpox, but also against other zoonotic orthopoxvirus infections, such as monkeypox, cowpox, buffalopox, and camel pox. All of them pose an represent increasing threat to human health and heighten a risk of emerging highly contagious viruses due to natural evolution of previous zoonotic orthopoxviruses. In order to prevent development of small outbreaks into spreading epidemics and, thus, to decrease a risk of emergence due to natural evolution of highly pathogenic for humans orthopoxviruses, efforts should be applied to develop safe new generation live vaccines based on vaccinia virus with target virulence genes inactivation. These strains should be examined in laboratory animal models inoculated via different routes. Currently, vaccinia virus often becomes attenuated to create live recombinant vaccines due to inserting target DNA sequences into the virus virulence genes resulting in their inactivation. Vaccinia virus strain LIVP used in the Russian Federation as smallpox vaccine as well as derivative attenuated variant LIVP-GFP created by using genetic engineering methods with inactivating its thymidine kinase gene were examined.Such viruses were intracerebrally inoculated into suckling mice at doses of 101 or 102 PFU/animal for neurovirulence assessment. Adult mice were infected intranasally, subcutaneously or intradermally at doses of 107 or 108 PFU/animal and clinical manifestations were analyzed for 14 days. On 28 day after the onset, blood serum samples were collected from individual mice to measure virus specific antibody level by using ELISA. It was shown that recombinant vaccinia virus strain LIVP-GFP displayed markedly lowered neurovirulence and pathogenicity for mice as compared to parental LIVP. Finally, intradermal route turned out to demonstrate the most safe and effective profile for immunization with both examined vaccinia virus strains.


2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Ivaylo Gentschev ◽  
Ulrike Donat ◽  
Elisabeth Hofmann ◽  
Stephanie Weibel ◽  
Marion Adelfinger ◽  
...  

Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. In the current study, we analyzed the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 against two human prostate cancer cell lines DU-145 and PC-3 in cell culture and in tumor xenograft models. By viral proliferation assays and cell survival tests, we demonstrated that GLV-1h68 was able to infect, replicate in, and lyse these prostate cancer cells in culture. In DU-145 and PC-3 tumor xenograft models, a single intravenous injection with GLV-1h68 resulted in a significant reduction of primary tumor size. In addition, the GLV-1h68-infection led to strong inflammatory and oncolytic effects resulting in drastic reduction of regional lymph nodes with PC-3 metastases. Our data documented that the GLV-1h68 virus has a great potential for treatment of human prostate carcinoma.


1999 ◽  
Vol 73 (4) ◽  
pp. 2863-2875 ◽  
Author(s):  
Sabine Röttger ◽  
Friedrich Frischknecht ◽  
Inge Reckmann ◽  
Geoffrey L. Smith ◽  
Michael Way

ABSTRACT The intracellular enveloped form of vaccinia virus (IEV) induces the formation of actin tails that are strikingly similar to those seen in Listeria and Shigella infections. In contrast to the case for Listeria and Shigella, the vaccinia virus protein(s) responsible for directly initiating actin tail formation remains obscure. However, previous studies with recombinant vaccinia virus strains have suggested that the IEV-specific proteins A33R, A34R, A36R, B5R, and F13L play an undefined role in actin tail formation. In this study we have sought to understand how these proteins, all of which are predicted to have small cytoplasmic domains, are involved in IEV assembly and actin tail formation. Our data reveal that while deletion of A34R, B5R, or F13L resulted in a severe reduction in IEV particle assembly, IEVs formed by the ΔB5R and ΔF13L deletion strains, but not ΔA34R, were still able to induce actin tails. The ΔA36R deletion strain produced normal amounts of IEV particles, although these were unable to induce actin tails. Using several different approaches, we demonstrated that A36R is a type Ib membrane protein with a large, 195-amino-acid cytoplasmic domain exposed on the surface of IEV particles. Finally, coimmunoprecipitation experiments demonstrated that A36R interacts with A33R and A34R but not with B5R and that B5R forms a complex with A34R but not with A33R or A36R. Using extracts from ΔA34R- and ΔA36R-infected cells, we found that the interaction of A36R with A33R and that of A34R with B5R are independent of A34R and A36R, respectively. We conclude from our observations that multiple interactions between IEV membrane proteins exist which have important implications for IEV assembly and actin tail formation. Furthermore, these data suggest that while A34R is involved in IEV assembly and organization, A36R is critical for actin tail formation.


Gene ◽  
1986 ◽  
Vol 49 (2) ◽  
pp. 207-213 ◽  
Author(s):  
Elizabeth M. Wilson ◽  
Walter M. Hodges ◽  
Dennis E. Hruby

Virus Genes ◽  
1993 ◽  
Vol 7 (1) ◽  
pp. 83-88 ◽  
Author(s):  
Kazufumi Hiramatsu ◽  
Kazuaki Mannen ◽  
Kumato Mifune ◽  
Akira Nishizono ◽  
Yoshiko Takita-Sonoda

2006 ◽  
Vol 54 (2) ◽  
pp. 103 ◽  
Author(s):  
Jong Young Oh ◽  
Byeong Ho Park ◽  
Myong Jin Kang ◽  
Jin Han Cho ◽  
Jong Cheol Choi ◽  
...  

2018 ◽  
Vol 11 (2) ◽  
pp. 41-51 ◽  
Author(s):  
I. Ya. Lukasevich

The subject of the research is new tools for business financing using the initial coin offering (ICO) in the context of the development of cryptocurrencies and the blockchain technologies as their basis. The purpose of the work was to analyze the advantages and disadvantages of the ICO in comparison with traditional financial tools as well as prospects, limitations and problems of using digital financial tools. Conclusions are made in relation to possibilities, limitations and application areas of digital business financing tools, particularly in the real sector, taking into account the specifics of the Russian economy and legislation. It is shown that the main problems of using the digital financial tools are related to the economic sphere and caused by the lack of adequate approaches to evaluation of assets as well as the shortage of objective information. The problems and new tasks of corporate finance in the digital economy are defined.


1988 ◽  
Vol 62 (1) ◽  
pp. 176-180 ◽  
Author(s):  
S L Hu ◽  
G D Plowman ◽  
P Sridhar ◽  
U S Stevenson ◽  
J P Brown ◽  
...  

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