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THIRD WORLD NETWORK BIOSAFETY INFORMATION SERVICE 19 May 2005 Some poxviruses are very attractive as live GE vaccine vectors for humans, domestic animals and wildlife, for use in vaccination against contagious diseases and cancers and recently also against fertility in pest animals. There are more than 100 such vaccines in different stages of clinical and field trials at the moment. The use of avipoxviruses as transgenic vaccine vectors are highly advocated as safe alternatives with high potential efficacy. Avipoxviruses have been chosen because they have a large genome that allows for insertion of many foreign genes and have a restricted host range. In particular, the restricted host range of avipoxviruses makes them the most attractive poxviruses for use as recombinant vaccines in humans. To date, little is known about the morphogenesis (development of form and structure as a result of growth and differentiation of cells) of avipoxviruses in mammalian cells. Limited numbers of avipoxviruses (fowlpox, canarypox, pigeonpox and penguinpox viruses) have been tested in infections of a few number of mammalian species and cell lines of mammalian origin. Neither have the prospects of recombination between GE avipox vectors and naturally occurring avipoxvirus species been extensively examined. Furthermore, knowledge concerning the number of species, strains or variants that exist within the genus Avipoxvirus is limited. Although all these questions remain to be answered, the prevailing view and the basis for biosafety claims of the use of avipoxviruses as GE vaccine vectors is that avipoxviruses cannot multiply in cells of mammalian origin. This paper clearly shows that the dogma does not hold water. The scientists show that avipoxvirus can multiply in a mammalian cell line, without interruption in the virus morphogenesis. They investigated the potentials of avipoxviruses (one reference fowlpoxvirus and two newly isolated strains from sparrow and pigeon) to multiply and produce infectious viral particles in two avian and eight mammalian cell lines. As expected, all three virus strains multiplied in both the avian cell lines. However, to their surprise, the scientists demonstrated multiplication of infectious avipoxvirus particles and observed various forms of infectious virus particles, in BHK-21 cells, from the Syrian hamster cell line. This was true for all the avipoxvirus strains. Electron microscopy was used to confirm the multiplication of avipoxvirus in mammalian cells. All the viral developmental stages that lead to the production of an infectious virus were observed in BHK-21 cells. Safety should be of paramount importance when considering GE vaccine vectors. Avipoxviruses, which should meet stringent criteria, need to be tested properly for their ability to establish productive infection in cells of mammalian origin. Furthermore, the vaccination of "free-ranging" human and animal recipients with a live GE virus vector is equal to deliberate release of that GE virus into the environment. Vaccination with live GE virus vectors should therefore be regulated as a deliberate release of a GMO. The abstract of the paper is attached below. With best wishes, Lim Li Ching Third World Network REF: Doc.TWN/Biosafety/2004/D Item 1 Virus Research 109 (2005) 39–49 Avipoxvirus multiplication in a mammalian cell line Simon Chioma Welia,∗,1, Øivind Nilssenb, Terje Traavika,c a Department of Microbiology
and Virology, b Department of Medical
Genetics, c Norwegian Received 17 June 2004; received in revised form 7 October 2004; accepted 7 October 2004 Available online 26 November 2004 Abstract Avipoxviruses have many advantages and are being increasingly employed as recombinant vaccine vectors. One attractive feature is that while inserted transgenes are expressed in immunologically favourable ways, avipoxvirus infections of mammalian cells are believed to be abortive. The experimental evidence supporting this belief is, however, based on a limited number of mammalian cell-types and a few avipoxvirus species. We evaluated two avian and eight mammalian cell lines for permissivity to three avipoxvirus strains, one reference fowlpoxvirus and two newly isolated strains from sparrow and pigeon, respectively. Both avian cell lines were, as expected, permissive for all three avipoxvirus strains. However, by multiplication assays, we found to our surprise that Syrian baby hamster kidney (BHK-21) cells were equally permissive to all virus strains. Results from electron microscopy of infected BHK-21 cells revealed viral morphogenesis proceeding to various forms of infectious viruses. These results were supported by the demonstration of avipoxvirus specific late gene expression and avipoxvirus specific DNA restriction pattern in BHK-21 infected cells. Keywords: Syrian baby hamster kidney; Avipoxvirus; DNA; Safety
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