A novel bivalent vaccine to prevent both Salmonella Typhi and Paratyphi infections: preclinical proof of concept

Dr Christine Rollier, Research Scientist
University of Oxford (UK)
Christine Rollier


Collaborators:
Dr Savitha Nagaraj, St John's Research Institute (India)
Dr Carl Britto, University of Oxford (UK)
Professor Andrew J Pollard, University of Oxford (UK)
Dr Mary Dias, St John's Research Institute (India)
Dr Christina Dold, University of Oxford (UK)

SUMMARY
Our aim is to develop a novel vaccine against two bacterial infections, together causing a large proportion of enteric fever cases in low-and-middle-income countries: typhoid and paratyphoid. Disease caused by these bacteria is a major global-health problem responsible for up to 21.6 million cases and 216,510 deaths annually. The established typhoid vaccines, Ty21a and Vi polysaccharide, have moderate efficacy, low immunogenicity in infants, and little evidence of efficacy beyond three years from vaccination. Recently WHO-recommended new typhoid conjugate vaccines may solve many of these issues but there remains no vaccine to prevent the substantial paratyphoid disease burden in Asia. Moreover, strains of bacteria resistant to antibiotics are emerging and disseminating globally, thus posing a real threat to the affected populations. Importantly, high cost is a limiting factor for wide use of vaccines in low-income countries, therefore a bivalent vaccine targeting both infections would be a particularly suited approach to improving health in the affected areas. We have selected two components common to both the typhoid and paratyphoid bacteria, and have already demonstrated that each component is able to induce strong immune responses when formulated in our proprietary vaccine technology. In this project, we will create a bivalent construct and investigate if the vaccine is able to protect against infection in animal models. In parallel, through a collaboration with St. John’s Research Institute, India, we will characterize the response induced by our selected antigens in the populations most affected by typhoid and paratyphoid fever in India during natural infection and re-infections, as this is essential to understanding the potential of our vaccine approach. 

If successful, the outcome of this project will be a vaccine formulation that can be progressed to clinical development, and the data generated will be used to leverage funding for GMP production and a phase I trial.