Immunity safety and protection of an Adenovirus-Prime:MVA-Boost vaccine against Mycobacterium avium subspecies paratuberculosis infection in calves

点击翻译按钮获取中文摘要

Mycobacterium avium subspecies paratuberculosis (MAP) is the bacterium that causes a chronic inflammation of the gut known as Johne's disease (JD) in many animals. JD is of significant economic importance to the management of cattle, sheep and goats due to loss in milk production and the need for premature culling when the disease becomes advanced; the cost has been estimated to be $1.5billion pa. in the USA and £13million pa. in the UK. Current measures to control the spread of JD have been shown to be inadequate and at present more than half of cattle herds in the UK are infected and nearly all herds in some other developed countries, including the USA. MAP is excreted in very large amounts in later stages of infection but can also be excreted even when current vaccines are used. This has led to the spread of MAP into wildlife reservoirs and contamination of environmental reservoirs such as rivers and lakes. MAP is excreted by infected dairy cattle in their milk and is present in supermarket milk as it survives pasteurization. There is an increasingly convincing link between MAP infection and Crohn's disease in humans, MAP has been detected in up to half of normal human intestinal samples and nearly all of Crohn's Disease samples. Currently, commercially available whole cell vaccines do not provide complete protection against JD. They may relieve clinical symptoms but do not significantly reduce the number of animals that are infected or stop excretion of MAP into milk and faeces. By allowing the induction of sub-clinical infection, these vaccines may hide the problem of MAP infection and consequently be counterproductive. Therefore, there is an urgent need to develop a better vaccine to treat this disease and to understand the way that MAP affects the animal's immune system to cause JD. This project will study a new type of vaccine that has been shown to work in mice. It uses two viruses that will not grow in animals or the environment, to deliver a cocktail of MAP antigens called HAV. Although vaccination trials in mice do not always transfer successfully to other animal species, results from preliminary experiments have shown that the prime-boost vaccination method we are proposing to use has been beneficial in conferring a degree of protection against other mycobacterial infections. We will look at the ability of the HAV vaccine to prevent an experimental infection of calves with MAP and measure in detail the cattle's immune system with the aim of understanding how this new type of vaccine might be working. This work will improve our knowledge of mycobacterial disease processes and could therefore also benefit other related research such as vaccines for tuberculosis for example. If the study does show that the new vaccine may be protective it could be a first step in improving the control of this increasingly spreading disease.