Bacterial Antigen Expression Is an Important Component in Inducing an Immune Response to Orally Administered Salmonella-Delivered DNA Vaccines

BACKGROUND: The use of Salmonella to deliver heterologous antigens from DNA vaccines is a well-accepted extension of the success of oral Salmonella vaccines in animal models. Attenuated S. typhimurium and S. typhi strains are safe and efficacious, and their use to deliver DNA vaccines combines the advantages of both vaccine approaches, while complementing the limitations of each technology. An important aspect of the basic biology of the Salmonella/DNA vaccine platform is the relative contributions of prokaryotic and eukaryotic expression in production of the vaccine antigen. Gene expression in DNA vaccines is commonly under the control of the eukaryotic cytomegalovirus (CMV) promoter. The aim of this study was to identify and disable putative bacterial promoters within the CMV promoter and evaluate the immunogenicity of the resulting DNA vaccine delivered orally by S. typhimurium. METHODOLOGY/PRINCIPAL FINDINGS: The results reported here clearly demonstrate the presence of bacterial promoters within the CMV promoter. These promoters have homology to the bacterial consensus sequence and functional activity. To disable prokaryotic expression from the CMV promoter a series of genetic manipulations were performed to remove the two major bacterial promoters and add a bacteria transcription terminator downstream of the CMV promoter. S. typhimurium was used to immunise BALB/c mice orally with a DNA vaccine encoding the C-fragment of tetanus toxin (TT) under control of the original or the modified CMV promoter. Although both promoters functioned equally well in eukaryotic cells, as indicated by equivalent immune responses following intramuscular delivery, only the original CMV promoter was able to induce an anti-TT specific response following oral delivery by S. typhimurium. CONCLUSIONS: These findings suggest that prokaryotic expression of the antigen and co-delivery of this protein by Salmonella are at least partially responsible for the successful oral delivery of C-fragment DNA vaccines containing the CMV promoter by S. typhimurium

Applications of Animal Models of Infectious Arthritis in Drug Discovery: A focus on Alphaviral Disease

Animal models, which mimic human disease, are invaluable tools for understanding the mechanisms of disease pathogenesis and development of treatment strategies. In particular, animal models play important roles in the area of infectious arthritis. Alphaviruses, including Ross River virus (RRV), o'nyong-nyong virus, chikungunya virus (CHIKV), mayaro virus, Semliki Forest virus and sindbis virus, are globally distributed and cause transient illness characterized by fever, rash, myalgia, arthralgia and arthritis in humans. Severe forms of the disease result in chronic incapacitating arthralgia and arthritis. The mechanisms of how these viruses cause musculoskeletal disease are ill defined. In recent years, the use of a mouse model for RRV-induced disease has assisted in unraveling the pathobiology of infection and in discovering novel drugs to ameliorate disease. RRV as an infection model has the potential to provide key insights into such disease processes, particularly as many viruses, other than alphaviruses, are known to cause infectious arthritides. The emergence and outbreak of CHIKV in many parts of the world has necessitated the need to develop animal models of CHIKV disease. The development of non-human primate models of CHIKV disease has given insights into viral tropism and disease pathogenesis and facilitated the development of new treatment strategies. This review highlights the application of animal models of alphaviral diseases in the fundamental understanding of the mechanisms that contribute to disease and for defining the role that the immune response may have on disease pathogenesis, with the view of providing the foundation for new treatmentOffice of the Snr Dep Vice Chancellor, Institute for GlycomicsNo Full Tex

Case study–crown prosecution of a British citizen for the extraterritorial murder of Sergeant First Class Randy Johnson, United States 2nd Cavalry Regiment

‘Make me comfortable’ were the last words of Sergeant First Class Randy Johnson of the United States 2nd Stryker Cavalry Regiment. The investigation into his murder would take seven years, span three countries, and involve forensic and technical exploitation analysis in the United States and the United Kingdom. The purpose of this case study is to discuss the unique aspects of battlefield forensic science and key factors that can lead to the prosecution of foreign terrorist fighters to meet obligations under United Nations Security Council Resolution 2396 (2017) and 2322 (2016) for member states to investigate foreign terrorist fighters

An overview of biosecurity in Australia

Threats of natural and deliberate biological agent release are very real and are of serious concern within Australia and internationally, having the potential to substantially impact human, plant and animal health as well as agriculture, trade relations, infrastructure and the economy. Biosecurity programmes and policies are essential for counteracting these threats and enabling a nation to effectively prevent and/or respond to the natural, accidental and deliberate release of a biological agent. The major biosecurity focus in Australia is the protection against invasive animal, plant and insect species; however, more recently, the threat of microbiological agents has become a priority for Australia's national security. Australia's biosecurity capabilities are maintained through a coordinated effort, involving national, state and local government and non-government agencies. Communication and collaboration between all parties, at both a national and international level, is the key to an effective response. The threat from biological agents is a very real concern and Australia must maintain its preparedness in order to ensure its capacity to respond to biological threats. This review provides a contemporary overview of biosecurity in Australia and the role of forensic science in the investigation of biosecurity incidents

The medicinal chemistry of dengue fever

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