Harnessing the structural flexibility of bovine monoclonal antibodies for the treatment of emerging virus infections

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Emerging virus infections such as Ebola and Lassa Fever virus are highly dangerous and result in significant illness and death. Outbreaks of these are set to increase in the future so it is crucial that we have effective and safe ways to treat infected individuals, for when outbreaks occur. Monoclonal antibodies have very potent antiviral activity but the virus can escape from their effects by mutating. This is particularly true for the majority of antibodies raised in mice and humans. This is because these antibodies predominately bind to highly exposed regions of the virus - regions that the virus can change without losing its ability to infect. However, some parts of the virus are more genetically conserved as they are directly involved in the infection pathway. These regions represent a vulnerability to the virus so it hides them away from antibody surveillance using the overall 'bulk' of the protein or by using sugars to hide them. Some animals, for example cattle, produce unusually large antibodies that are able to directly interact with these hidden regions so the virus cannot easily escape from them. We have developed a method to allow us to generate monoclonal antibodies from cattle and we will use this to develop a new class of therapies to target some of the most important emerging virus infections. We will use the surface proteins of Ebola, Lassa Fever, Nipah and Marburg virus to immunise cattle then use recombinant DNA techniques to produce antibodies, which we can screen for their ability to neutralise different strains of each virus. Ultimately, those antibodies showing the most potent and broad antiviral activity can be progressed into clinical development for use in human outbreaks.