title: Humanized monoclonal antibody 2C9-cIgG has enhanced efficacy for yellow fever prophylaxis and therapy in an immunocompetent animal model.
abstract: Yellow fever virus (YFV) causes significant human disease and mortality in tropical regions of South and Central America and Africa, despite the availability of an effective vaccine. No specific therapy for YF is available. We previously showed that the humanized monoclonal antibody (MAb) 2C9-cIgG provided prophylactic and therapeutic protection from mortality in interferon receptor-deficient strain AG129 mice challenged with YF 17D-204 vaccine. In this study we tested the prophylactic and therapeutic efficacy of this MAb against virulent YFV infection in an immunocompetent hamster model. Intraperitoneal (ip) administration of a single dose of MAb 2C9-cIgG 24h prior to YFV challenge resulted in significantly improved survival rates in animals treated with 380 or 38 μg of MAb compared to untreated animals. Treatment with the higher dose also resulted in significantly improved weight gain and reductions in serum alanine aminotransferase (ALT) and virus titers in serum and liver. Prophylactic treatment with 2C9-cIgG 24h prior to virus challenge prevented the development of a virus-neutralizing antibody (vnAb) response in hamsters. Administration of a single ip dose of 380 μg of 2C9-cIgG as late as 72 h post-YFV challenge also resulted in significant improvement in survival rates. Hamsters treated at 4-72 h post-virus challenge developed a robust vnAb response. Enhanced survival and improvement of various disease parameters in the hamster model when MAb 2C9-cIgG is administered up to 3 days after virus challenge demonstrate the clinical potential of specific antibody therapy for YF.
authors.affiliation: Institute for Antiviral Research, Utah State University, Logan, UT 84322, USA.
authors.forename: Justin G
authors.initials: JG
authors.lastname: Julander
authors.affiliation: Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA; Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Thibodeaux
authors.affiliation: Institute for Antiviral Research, Utah State University, Logan, UT 84322, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Morrey
authors.affiliation: Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Roehrig
authors.affiliation: Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA. Electronic address: cblair@colostate.edu.
authors.forename: Carol D
authors.initials: CD
authors.lastname: Blair
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000627:therapeutic use*; D001835:Body Weight; D006224:Cricetinae; D004195:Disease Models, Animal; D007116:Immunization, Passive / Q000379:methods*; D008099:Liver / Q000821:virology; D008647:Mesocricetus; D044967:Serum / Q000821:virology; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load; D015004:Yellow Fever / Q000188:drug therapy* / Q000517:prevention & control*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000410:Alanine Transaminase
keywords: Hamster model; Humanized monoclonal antibody; Immunoprophylaxis; Immunotherapy; Yellow fever