Improved Vaccination Strategy - Isis Project No 1049

Research by Professor Vincenzo Cerundolo at the Institute of Molecular Medicine, University of Oxford has identified a method of vaccination using peptides and proteins that produces a powerful immune response that is specific to a broad range of tumour/viral epitopes.

THERAPEUTIC AREAS / APPLICATION

Induction of host immune responses, in particular to viruses and tumours

BACKGROUND

Prime/boost vaccination protocols based on repeated injections of the same antigen are able to generate strong cytotoxic T-lymphocyte (CTL) immune responses. However, during the priming stage of a vaccine regimen the more dominant epitopes of the antigen provoke a greater CTL response than the weaker epitopes – so called immunodominance. This skewing of the immune response is exacerbated a: in patients with a pre-existing natural immune response against an epitope encoded by the poly-epitope vaccine construct (e.g., HIV patients and late stage melanoma patients) and b: if the same poly-epitope construct is administered during the boosting phase.

The effect of immunodominance is that prime/boost vaccination strategies based on the use of poly-epitope constructs fail to expand a broad CTL response by favouring the proliferation of CTL expanded either during the individual’s natural immune response or in the initial priming stage.

THE OXFORD INVENTION

The Oxford inventors have devised a novel vaccination strategy that helps to overcome the potentially negative effect of immunodominance in conventional poly-epitope vaccines, and have shown that this improved regimen leads to the simultaneous expansion of dominant and subdominant CTL of multiple specificities to highly effective levels in vivo. This novel vaccination strategy can also be used to boost immune responses to epitopes such as those found on tumour cells and virus infected cells. Furthermore, the inventors have shown that this strategy enables use of peptides and proteins in the boosting stage, either alone or pulsed over the patient’s dendritic cells. This overcomes the risk of unwanted side effects associated with viral vectors and also means that it is no longer necessary to identify the exact epitopes against which an immune response is desired, nor to isolate DNA for those epitopes.

COMMERCIALISATION OPPORTUNITY

This excitingOxford technology is the subject of a patent application. Companies interested in product developments arising from this work are invited to contact Isis Innovation to discuss how they could utilise this technology.

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