Therapeutic neutralizing monoclonal antibody administration protects against lethal yellow fever virus infection
Michael J. Ricciardi, Lauren N. Rust, Núria Pedreño-López, Sofiya Yusova, Sreya Biswas, Gabriela M. Webb, Lucas Gonzalez-Nieto, Thomas B. Voigt, Johan J. Louw, Fernanda D. Laurino, John R. DiBello, Hans-Peter Raué, Aaron Barber-Axthelm, Kimberly Chun, Samantha Uttke, Lidiane Menezes Souza Raphael, Aaron Yrizarry-Medina, Brandon C. Rosen, Rebecca Agnor, Lina Gao, Caralyn S. Labriola, Michael K. Axthelm, Jeremy Smedley, Justin G. Julander, Myrna C. Bonaldo, Laura M. Walker, Ilhem Messaoudi, Mark K. Slifka, Dennis R. Burton, Esper G. Kallás, Jonah B. Sacha, David I. Watkins, Benjamin J. Burwitz
Abstract
Yellow fever virus (YFV) is a reemerging global health threat, driven by several factors, including increased spread of the mosquito vector and rapid urbanization. Although a prophylactic vaccine exists, vaccine hesitancy, supply deficits, and distribution difficulties leave specific populations at risk of severe YFV disease, as evidenced by recent outbreaks in South America. To establish a treatment for patients with severe YFV infection, we tested 37 YFV-specific monoclonal antibodies isolated from vaccinated humans and identified two capable of potently neutralizing multiple pathogenic primary YFV isolates. Using both hamster and nonhuman primate models of lethal YFV infection, we demonstrate that a single administration of either of these two potently neutralizing antibodies during acute infection fully controlled viremia and prevented severe disease and death in treated animals. Given the potential severity of YFV-induced disease, our results show that these antibodies could be effective in saving lives and fill a much-needed void in managing YFV cases during outbreaks.