Immunological responses to emerging phlebo- and arenaviruses

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Emerging New World arena- and phlebo-viruses are threats to human health for which there are no preventative vaccines or therapeutic treatments. Upon infection of a previously unexposed human host, such pathogens often cause rapid disease progression and result in high mortality rates. The viral glycoproteins displayed on the surface of these viruses are the primary determinants of the host immune response and thus lead targets in antiviral and vaccine design. The objective of this work is to study the antibody response against these viral glycoproteins, at a molecular level, with the aim of isolating and characterizing monoclonal antibodies that can target and prevent the virus infection cycle. A particular emphasis of this work is to isolate monoclonal antibodies, which can bind and (cross)-neutralise several biomedically important viruses from the same families. Following isolation of monoclonal antibodies, we will apply X-ray crystallography and other biophysical tools to define neutralising epitopes targeted on the virus surface. By analogy to the success in development of monoclonal antibody cocktails to treat Ebola virus infection, the data and reagents produced in this work will provide a platform by which to therapeutically target these dangerous groups of pathogens.