Live Variola Virus Considerations for Continuing Research (2009) / Chapter Skim
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10 Conclusions and Recommendations
10 Conclusions and Recommendations
Pages 131-138
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From page 131... ...
and international regulatory requirements for licensure of antiviral drugs and vaccines have become better defined; and technological advances in molecular biology have generated sophisticated tools for research and development, many of which have been applied to improving knowledge about variola virus. Given that an accidental or deliberate release of variola virus could have devastating results worldwide, current global public health preparedness efforts address the potential threat of a smallpox outbreak.
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From page 132... ...
These advances also offer potential benefits for the future development of variola countermeasures. In this contemporary context, some research with live variola virus remains essential for public health preparedness, some would be useful for this purpose, and some would have significant scientific merit as biomedical research without an immediate connection to preparedness.
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From page 133... ...
This undertaking will require a better understanding of variola-specific proteins and their functions in cultured cells and of how these gene products contribute to the pathogenesis of smallpox disease in suitable animal models. The committee concludes that, for both scientific and regulatory reasons, the final developmental stages leading to licensure of small pox therapeutics cannot occur without the use of live variola virus.
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From page 134... ...
Development of Methods for Detection and Diagnosis Contemporary nucleic acid-based methods for viral detection have been shown to identify variola virus genes directly, and multiplex PCR assays differentiate variola from other poxviruses and unrelated viruses, such as varicella-zoster virus, that may cause similar clinical signs. Since tissues contain inhibitors that may reduce the sensitivity and specificity of nucleic acid-based methods, the development of these assays is enhanced by the
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From page 135... ...
Protein-based assays have not been pursued as extensively as PCR methods; however, these methods can be tested using variola proteins made in expression vectors. Limited information has been published about the performance of any methods for environmental sampling to detect variola, but again such assessments do not require live variola virus.
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From page 136... ...
However, current methods for studying variola in vitro and in vivo are inadequate or have not been fully exploited for the expeditious discovery of novel interventions, both for smallpox and for other diseases, that might result from a better understanding of how this pathogen takes over human cells and subverts the immune response. Further research is needed to develop improved animal models that can recapitulate key aspects of the human disease and to understand virus–cell interactions in human target cells relevant to pathogenesis and immune response.
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From page 137... ...
Finally, functional genomics tools, which are used to evaluate interactions between a replicating virus and the host cell, should be applied using a few representative variola strains in a number of representative differentiated human cell types. The purpose of this research would be to identify novel targets for therapeutics and to design third-generation vaccines.
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