Journal Article

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

McElfresh, G.W., Ricciardi, Michael J., Ghosh, Noor, Godoy, Giovana, Watkins, David I., Panayiotou, Christakis, Webb, Gabriela, Axthelm, Michael, Bimber, Benjamin N., Yusova, Sofiya, Yrizarry-Medina, Aaron, Mauter, Jack T., Sacha, Jonah B., Kallas, Esper G., Zweig, Robert, Lutz, Savannah S., Smedley, Jeremy, Voigt, Thomas B., Louw, Johan J., Rust, Lauren N., Zilverberg, Gavin, Labriola, Caralyn S., Biswas, Sreya, Bailey, Lauren, Burwitz, Benjamin J., Tonelli, Rachael, Swanson, Tonya, Rosen, Brandon C., Fischer, Miranda, Barber-Axthelm, Aaron, Slifka, Mark K., Meanor, Jenna

2025

Overview

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 postinfection (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 i.v. 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 IFN, IL-6, 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.

• Publisher: American Society for Clinical Investigation,American Society for Clinical investigation
• Subject: Age / Animals / Antibodies, Monoclonal - administration & dosage / Antibodies, Monoclonal - pharmacology / Antibodies, Monoclonal - therapeutic use / Antibodies, Neutralizing - administration & dosage / Antibodies, Neutralizing - immunology / Antibodies, Neutralizing - pharmacology / Antibodies, Neutralizing - therapeutic use / Antibodies, Viral - administration & dosage / Antibodies, Viral - immunology / Chemokines / Clinical trials / Cytokines - metabolism / Disease Models, Animal / Epidemics / Female / Fever / Humans / Immunology / Infections / Infectious disease / Macaca mulatta / Male / Monoclonal antibodies / Monocyte chemoattractant protein 1 / Vaccines / Viremia / Yellow Fever - drug therapy / Yellow Fever - immunology / Yellow Fever - mortality / Yellow Fever - prevention & control / Yellow fever virus - drug effects / Yellow fever virus - immunology