Prophylactic and therapeutic neutralizing monoclonal antibody treatment prevents lethal yellow fever infection

Authors

• Lauren N. Rust, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• Michael J. Ricciardi, Mabloc LLC, Washington DC, United States of America.
• Savannah S. Lutz, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• Sofiya Yusova, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• Johan J. Louw, George Washington University, Washington DC, United States of America.
• Aaron Yrizarry-Medina, George Washington University, Washington DC, United States of America.
• Sreya Biswas, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• Miranda Fischer, Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, United States of America.
• Aaron Barber-Axthelm, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• Gavin Zilverberg, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• Lauren Bailey, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• Tonya Swanson, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• Rachael Tonelli, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• G W. McElfresh, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• Brandon C. Rosen, George Washington University, Washington DC, United States of America.
• Thomas B. Voigt, George Washington University, Washington DC, United States of America.
• Christakis Panayiotou, George Washington University, Washington DC, United States of America.
• Jack T. Mauter, George Washington University, Washington DC, United States of America.
• Noor Ghosh, George Washington University, Washington DC, United States of America.
• Jenna Meanor, George Washington University, Washington DC, United States of America.
• Giovana Godoy, George Washington University, Washington DC, United States of America.
• Michael Axthelm, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• Jeremy Smedley, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• Mark K. Slifka, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• Esper G. Kallas, Department of Infectious Diseases and Tropical Medicine, School of Medicine, University of São Paulo, São Paulo, Brazil.
• Gabriela Webb, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• Robert Zweig, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• Caralyn S. Labriola, Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, United States of America.
• Benjamin N. Bimber, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• Jonah B. Sacha, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.
• David I. Watkins, Mabloc LLC, Washington DC, United States of America.
• Benjamin J. Burwitz, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States of America.

Document Type

Journal Article

Publication Date

7-15-2025

Journal

JCI insight

DOI

10.1172/jci.insight.191665

Keywords

Hepatitis; Immunology; Infectious disease; Therapeutics

Abstract

Yellow Fever virus (YFV) infection is fatal in 5-10% of the 200,000 yearly cases. There is currently no available antiviral treatment. We showed previously that administration of 50 mg/kg of a YFV-specific neutralizing monoclonal antibody (nmAb) at 2 days post-infection (dpi), prior to the onset of severe disease, protected YFV-infected rhesus macaques from death. To further explore the clinical applicability of our nmAb MBL-YFV-01, we treated rhesus macaques with a lower dose (10 mg/kg) of this nmAb prophylactically or therapeutically at 3.5 dpi. We show that a single prophylactic or therapeutic intravenous dose of our nmAb protects rhesus macaques from death following challenge. A comprehensive analysis of 167 inflammatory cytokine and chemokines revealed that protection was associated with significantly reduced expression of 125 of these markers, including type I interferons, IL6, and CCL2. This study further expands the potential clinical use of our YFV-specific nmAb, which could be used during an outbreak for immediate prophylactic immunity or for patients with measurable serum viremia.

APA Citation

Rust, Lauren N.; Ricciardi, Michael J.; Lutz, Savannah S.; Yusova, Sofiya; Louw, Johan J.; Yrizarry-Medina, Aaron; Biswas, Sreya; Fischer, Miranda; Barber-Axthelm, Aaron; Zilverberg, Gavin; Bailey, Lauren; Swanson, Tonya; Tonelli, Rachael; McElfresh, G W.; Rosen, Brandon C.; Voigt, Thomas B.; Panayiotou, Christakis; Mauter, Jack T.; Ghosh, Noor; Meanor, Jenna; Godoy, Giovana; Axthelm, Michael; Smedley, Jeremy; Slifka, Mark K.; Kallas, Esper G.; Webb, Gabriela; Zweig, Robert; Labriola, Caralyn S.; Bimber, Benjamin N.; Sacha, Jonah B.; Watkins, David I.; and Burwitz, Benjamin J., "Prophylactic and therapeutic neutralizing monoclonal antibody treatment prevents lethal yellow fever infection" (2025). GW Authored Works. Paper 7590.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7590

Department

Pathology