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Towards the development of antistaphylococcal immunotherapy

PhD ceremony:Mr D.G.A.M. (Danny) Koedijk
When:June 21, 2017
Start:11:00
Supervisor:prof. dr. J.M. (Jan Maarten) van Dijl
Co-supervisor:dr. ing. G. (Girbe) Buist
Where:Academy building RUG
Faculty:Medical Sciences / UMCG

The World Health Organization predicts that infections caused by antibiotic resistant microbes will be the number one cause of deaths in 2050. Accordingly, methicillin-resistant Staphylococcus aureus (widely known as MRSA), was recently ranked 5th on the “WHO priority pathogens list” as a target for new antimicrobial therapies. Indeed, infections by MRSA are difficult to treat, and therefore new approaches for prevention and treatment of infections caused by this pathogen are urgently needed. Possible alternatives to antibiotics are active and passive immunization approaches, where patients are either vaccinated with the inactivated pathogen or some of the pathogen’s components,  or with antibodies from an appropriate donor source. The present PhD research describes a pipeline that can be applied to develop such active or passive immunization approaches to protect frail individuals against infections by MRSA. Particular attention was attributed to proteins exposed on the surface of MRSA, especially a protein named IsaA. The developed pipeline was used to produce the IsaA protein for active immunization against MRSA, and a monoclonal antibody against IsaA for passive immunization. The results show that active vaccination with pure IsaA is challenging, possibly because the immune system may recognize the wrong end of this protein. However, at least in an animal model, the anti-IsaA antibody gives partial protection against S. aureus infection. Altogether, these results show that the pipeline that was developed to purify MRSA proteins and to raise antibodies against them represents a promising step towards the development of anti-MRSA immunotherapy.