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

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.

Department

Pathology

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