Adenovirus-Mediated Gene Therapy Against Viral Biothreat Agents
Defence Research and Defence Canada- Suffield Medicine Hat, Alberta Canada
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The common features of viral biothreat agents are highly lethal, easy to grow, and transmissible by aerosol. The examples of viral diseases caused by these agents are smallpox, viral hemorrhagic fevers, and viral encephalitis together with newly emerged viral diseases such as severe acute respiratory syndrome SARS and avian influenza. A deliberate release of these agents on general public or a natural outbreak could pose a great threat to the public health and global economy. Vaccine development is an important strategy to thwart the threat of these viral biothreat agents. There is an urgent need to improve existing vaccines against these agents and to develop new ones. Gene therapy, which introduces therapeutic genes into mammalian cells to achieve therapeutic effective, has a great potential for use as a defensive strategy against viral biothreat agents. Viral vectors that are developed in gene therapy for delivering therapeutic genes can be used for the development of vaccines against viral biothreat agents. Genes encoding protective antigens of viral biothreat agents can be carried by these viral vectors and be expressed to induce an immune response. The successful and safe use of an adenovirus vaccine to protect military trainees from acute respiratory disease has led to modify adenoviruses as vectors for vaccine development against other viral agents. Human adenovirus serotype 5 HAd5 is the most commonly used adenovirus serotype for constructing vaccines because of its low virulence, strong induction of both humoral and cellular immunities and ease of growth in cell culture. This chapter will describe the use of HAd5 vector for the development of vaccines against viral hemorrhagic fevers, viral encephalitis, SARS and avian influenza.