Infection by rabies virus causes about 40,000-70,000 deaths per year worldwide. More than 99% of all human deaths occur in Africa, Asia and South America, most commonly involving children aged under 15 years. The recommended therapeuthic procedure for peop le suspected to be infected with this virus includes the immediate administration of both vaccine and rabies specific immunoglobulins (RIG). Prophylaxis in the form of immunoglobulins includes equine anti-rabies immunoglobulins (ERIG) or human anti-rabies Ig (HRIG), however these reagents are expensive, and in short supply especially in developing countries. One solution that is being explored is to generate a cocktail of rabies neutralising monoclonal antibodies to replace ERIG. If it were possible to gene rate enough recombinant antibodies cheaply, then this would be of enormous benefit in rabies affected countries, particularly in SE Asia and Africa In this proposal we aim to select new and cross- neutralising antibodies against lyssavirus strains using re combinant antibody phage-display technology. Two single chain Fv antibody phage display libraries will be used, a human naïve library and a synthetic murine scFv library derived from a stable protein scaffold. The selected scFvs will be tested for in vitro virus neutralization assays and up to two antibodies will be chosen for engineering back into the heavy and light chains of a human Ig, generating chimeric anti rabies Mabs. The engineered antibodies will initially be introduced into tobacco plants to as sess plant expression in plants. Ultimately, the aim is to use transgenic maize expression, but this is beyond the scope of the current application.
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