Isolation of a Potently Neutralizing and Protective Human Monoclonal Antibody Targeting Yellow Fever Virus
Michael P. Doyle, Joseph R. Genualdi, Adam L. Bailey, Nurgun Kose, Christopher Gainza, Jessica Rodríguez, Kristen M. Reeder, Christopher A. Nelson, Prashant N. Jethva, Rachel E. Sutton, Robin Bombardi, Michael L. Gross, Justin G. Julander, Daved H. Fremont, Michael Diamond, James E. Crowe
Abstract
Yellow fever virus (YFV) is a mosquito-borne virus that occasionally causes outbreaks of severe infection and disease in South America and sub-Saharan Africa. There are very effective live-attenuated (weakened) yellow fever virus vaccines, but recent problems with their production and distribution have left many people in affected areas vulnerable. Here, we sought to isolate an antibody targeting the surface of the virus for possible use in the future as a biologic drug to prevent or treat YFV infection. We isolated naturally occurring antibodies from individuals who had received a YFV vaccine. We created antibodies and tested them. We found that the antibody with the most powerful antiviral activity was a beneficial treatment in two different small-animal models of human infection. These studies identified features of the virus that are recognized by the human immune system and generated a therapeutic antibody candidate that inhibits infection caused by highly virulent strains of YFV.