Biomedical Catalyst – Staphylococcus aureus Vaccine

S. aureus is a bacterium that colonises the nasal lining and skin of >30% of people. Accidents, surgery or device implantation that breach natural barriers, allow invasion, which may result in life-threatening infections such as pneumonia and blood-borne infections particularly by the antibiotic resistant form (MRSA). Despite several attempts S. aureus no vaccine is yet available. All vaccine clinical trials have failed despite promising pre-clinical animal model data. The partners and subcontractors in this project led by Absynth Biologics Limited and the University of Sheffield are bringing together capabilities to address this problem namely: novel vaccine targets and technologies to more effectively stimulate the human immune system. This coupled with a greater understanding of the development of infection (physiological and immunological) will be used innovatively to select the best candidate vaccine for clinical development.

S. aureus is a bacterium that colonises the nasal lining and skin of >30% of people. Accidents, surgery or device implantation that breach natural barriers, allow invasion, which may result in life-threatening infections such as pneumonia and blood-borne infections particularly by the antibiotic resistant form (MRSA). Despite several attempts S. aureus no vaccine is yet available. All vaccine clinical trials have failed despite promising pre-clinical animal model data. The partners and subcontractors in this project led by Absynth Biologics Limited and the University of Sheffield are bringing together capabilities to address this problem namely: novel vaccine targets and technologies to more effectively stimulate the human immune system. This coupled with a greater understanding of the development of infection (physiological and immunological) will be used innovatively to select the best candidate vaccine for clinical development.

The University of Sheffield research team will be core to the overall programme, participating throughout its tenure. Specifically we will be responsible for determining the correlates of disease such that successful vaccination regimes can be evaluated. In part this will involve analysis of infection dynamics by monitoring how bacterial populations change during disease progression. Our preliminary work has already revealed a bottleneck, such that single bacteria go on to found abscesses. Being able to target these founders will prevent the population expansion that can lead to serious later consequences for the host. The use of animal models of infection and vaccination are at the heart of the programme as without these one cannot determine vaccine efficacy. In Sheffield two complementary pathogenesis models will be used (sepsis and peritonitis) within which the correlates of disease will be determined (such as weight loss and specific immune response) in order to elucidate those parameters that are markers of infection. Onto these findings the vaccine candidates produced by other members of the programme will be evaluated. The Sheffield work will be set within the context of the ongoing studies of all partners and contractors. An integrated programme will ensure that the fundamental results from Sheffield will immediately be translated into vaccine development.
The anticipated outcome of the programme is proof of concept to support the advance of the vaccine to clinical trials by Absynth and/or a corporate partner. A vaccine to prevent S. aureus infections and the scourge of drug resistant MRSA will have a great impact with associated healthcare, societal and financial implications.