Isolation of a potently neutralizing and protective human monoclonal antibody targeting yellow fever virus

Michael P Doyle, Vanderbilt University
Joseph R Genualdi, Vanderbilt University
Adam L Bailey, Washington University School of Medicine in St. Louis
Nurgun Kose, Vanderbilt University
Christopher Gainza, Vanderbilt University
Jessica Rodriguez, Vanderbilt University
Kristen M Reeder, Vanderbilt University
Christopher A Nelson, Washington University School of Medicine in St. Louis
Prashant N Jethva, Washington University in St. Louis
Rachel E Sutton, Vanderbilt University
Robin G Bombardi, Vanderbilt University
Michael L Gross, Washington University in St. Louis
Justin G Julander, Utah State University
Daved H Fremont, Washington University School of Medicine in St. Louis
Michael S Diamond, Washington University School of Medicine in St. Louis
James E Crowe, Vanderbilt University


Yellow fever virus (YFV) causes sporadic outbreaks of infection in South America and sub-Saharan Africa. While live-attenuated yellow fever virus vaccines based on three substrains of 17D are considered some of the most effective vaccines in use, problems with production and distribution have created large populations of unvaccinated, vulnerable individuals in areas of endemicity. To date, specific antiviral therapeutics have not been licensed for human use against YFV or any other related flavivirus. Recent advances in monoclonal antibody (mAb) technology have allowed the identification of numerous candidate therapeutics targeting highly pathogenic viruses, including many flaviviruses. Here, we sought to identify a highly neutralizing antibody targeting the YFV envelope (E) protein as a therapeutic candidate. We used human B cell hybridoma technology to isolate mAbs from circulating memory B cells from human YFV vaccine recipients. These antibodies bound to recombinant YFV E protein and recognized at least five major antigenic sites on E. Two mAbs (designated YFV-136 and YFV-121) recognized a shared antigenic site and neutralized the YFV-17D vaccine strain