Development of a Live Attenuated Vaccine Against Salmonella Paratyphi (VASP)

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Enteric fever is a disease affecting more than 20 million people every year and is a particular problem for young children. Two types of Salmonella cause the diseases, typhoid and paratyphoid, and while there is a vaccine available for typhoid, there is no vaccine for paratyphoid. Paratyphoid affects more than 5 million people annually, and accounts for 50% of cases of enteric fever in returning travellers in the UK. Paratyphoid is expected to become the main cause of enteric fever following the roll out of new generation of typhoid vaccines in the next few years. There is also a fear that paratyphoid is important in antibiotic resistance and could take over the place of typhoid and become more common but not preventable and with reduced options for treatment as a result of antibiotic resistance. There are no licensed paratyphoid vaccines but we have recently shown in n MRC research project that individuals experimentally infected with paratyphoid can become resistant to reinfection. We have therefore proposed testing a weakened strain of paratyphoid, which cannot cause disease, as a live vaccine to be taken by mouth. The vaccine has already been given to volunteers and shown to be safe and make an immune response. In this application we propose to manufacture this live attenuated vaccine (CVD 1902) under strict conditions and test it with volunteers to see if it can prevent infection. We will ask volunteers to take the vaccine by mouth in a drink and then, one month later, try and infect them with paratyphoid by getting them to drink the bacteria in a bicarbonate solution. If the vaccine works it will stop the volunteers developing early signs of paratyphoid (before we treat them). We will also study the immune responses to understand how the vaccine works to protect our volunteers. We will define whether CVD 1902 can provide protection and, if it does so, develop the vaccine for use to control this disease.