Rational identification of therapeutic targets against emerging arthritogenic alphaviruses

Arthritogenic alphaviruses are re-emerging mosquito-borne viruses that cause high fever and severe joint pain that may persist for years. Chikungunya virus, the most prominent arthritogenic alphavirus, has caused explosive outbreaks affecting millions of people world-wide. Currently, there are no available vaccines or specific drugs against the virus. Global spread of Aedes mosquito vectors underscores the potential emergence and threat of other alphaviruses. In this work, I will isolate and characterise monoclonal antibodies from volunteers in the Chikungunya virus vaccine trials to obtain large panel of highly neutralising human monoclonal antibodies against Chikungunya virus and broadly neutralising antibodies against multiple arthritogenic alphaviruses. I will combine complementary structural biology techniques to characterise these monoclonal antibodies to provide valuable insights into molecular basis for the human antibody response to vaccination and identify monoclonal antibodies candidate for therapeutic intervention against Chikungunya virus and emerging arthritogenic alphaviruses