title: A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 in vitro but does not protect a mouse model from disease.
abstract: The yellow fever virus (YFV) vaccine 17D-204 is considered safe and effective, yet rare severe adverse events (SAEs), some resulting in death, have been documented following vaccination. Individuals exhibiting post-vaccinal SAEs are ideal candidates for antiviral monoclonal antibody (MAb) therapy; the time until appearance of clinical signs post-exposure is usually short and patients are quickly hospitalized. We previously developed a murine-human chimeric monoclonal antibody (cMAb), 2C9-cIgG, reactive with both virulent YFV and 17D-204, and demonstrated its ability to prevent and treat YF disease in both AG129 mouse and hamster models of infection. To counteract possible selection of 17D-204 variants that escape neutralization by treatment with a single MAb (2C9-cIgG), we developed a second cMAb, 864-cIgG, for use in combination with 2C9-cIgG in post-vaccinal therapy. MAb 864-cIgG recognizes/neutralizes only YFV 17D-204 vaccine substrain and binds to domain III (DIII) of the viral envelope protein, which is different from the YFV type-specific binding site of 2C9-cIgG in DII. Although it neutralized 17D-204 in vitro, administration of 864-cIgG had no protective capacity in the interferon receptor-deficient AG129 mouse model of 17D-204 infection. The data presented here show that although DIII-specific 864-cIgG neutralizes virus infectivity in vitro, it does not have the ability to abrogate disease in vivo. Therefore, combination of 864-cIgG with 2C9-cIgG for treatment of YF vaccination SAEs does not appear to provide an improvement on 2C9-cIgG therapy alone.
authors.affiliation: Division of Vector-Borne Diseases, U.S. Centers for Disease Control and Prevention, Fort Collins, CO, 80521, USA.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Calvert
authors.affiliation: Division of Vector-Borne Diseases, U.S. Centers for Disease Control and Prevention, Fort Collins, CO, 80521, USA.
authors.forename: Kandice L
authors.initials: KL
authors.lastname: Dixon
authors.affiliation: Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, 80523-1692, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Piper
authors.affiliation: Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, 80523-1692, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Bennett
authors.affiliation: Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, 80523-1692, USA.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Thibodeaux
authors.affiliation: Department of Pathology and Sealy Center for Vaccine Development, University of Texas-Medical Branch, Galveston, TX, 77555, USA.
authors.forename: Alan D T
authors.initials: AD
authors.lastname: Barrett
authors.affiliation: Division of Vector-Borne Diseases, U.S. 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, 80523-1692, USA. Electronic address: carol.blair@colostate.edu.
authors.forename: Carol D
authors.initials: CD
authors.lastname: Blair
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology* / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000276:immunology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D007116:Immunization, Passive; D051379:Mice; D009500:Neutralization Tests; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism; D015004:Yellow Fever / Q000276:immunology* / Q000517:prevention & control* / Q000628:therapy; D022341:Yellow Fever Vaccine / Q000009:adverse effects / Q000276:immunology*; D015005:Yellow fever virus / Q000276:immunology*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D017471:Receptors, Interferon; D014759:Viral Envelope Proteins; D022341:Yellow Fever Vaccine
keywords: Monoclonal antibody therapy; Neutralizing antibody; Post-vaccinal SAE; YFV vaccine