Therapeutic neutralizing monoclonal antibody administration protects against lethal yellow fever virus infection

Michael J. Ricciardi, Mabloc LLC, 725 21st St. NW, Suite 301, Washington, DC 20052, USA.
Lauren N. Rust, Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA.
Nuria Pedreño-Lopez, George Washington University, 2121 I St. NW, Washington, DC 20052, USA.
Sofiya Yusova, Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA.
Sreya Biswas, Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA.
Gabriela M. Webb, Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA.
Lucas Gonzalez-Nieto, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Thomas B. Voigt, Mabloc LLC, 725 21st St. NW, Suite 301, Washington, DC 20052, USA.
Johan J. Louw, George Washington University, 2121 I St. NW, Washington, DC 20052, USA.
Fernanda D. Laurino, Mabloc LLC, 725 21st St. NW, Suite 301, Washington, DC 20052, USA.
John R. DiBello, Mabloc LLC, 725 21st St. NW, Suite 301, Washington, DC 20052, USA.
Hans-Peter Raué, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
Aaron M. Barber-Axthelm, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
Kimberly Chun, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
Samantha Uttke, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
Lidiane M. Raphael, Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Aaron Yrizarry-Medina, George Washington University, 2121 I St. NW, Washington, DC 20052, USA.
Brandon C. Rosen, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Rebecca Agnor, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
Lina Gao, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
Caralyn Labriola, Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA.
Michael Axthelm, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
Jeremy Smedley, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
Justin G. Julander, Institute for Antiviral Research, Utah State University, Logan, UT 84322, USA.
Myrna C. Bonaldo, Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Laura M. Walker, Adagio Therapeutics Inc., Waltham, MA 02451, USA.
Ilhem Messaoudi, Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY 40536, USA.
Mark K. Slifka, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
Dennis R. Burton, Mabloc LLC, 725 21st St. NW, Suite 301, Washington, DC 20052, USA.
Esper G. Kallas, Mabloc LLC, 725 21st St. NW, Suite 301, Washington, DC 20052, USA.
Jonah B. Sacha, Mabloc LLC, 725 21st St. NW, Suite 301, Washington, DC 20052, USA.
David I. Watkins, Mabloc LLC, 725 21st St. NW, Suite 301, Washington, DC 20052, USA.

Document Type

Journal Article

Publication Date

3-29-2023

Journal

Science translational medicine

Volume

15

Issue

689

DOI

10.1126/scitranslmed.ade5795

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.

Department

Pathology

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