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: Amanda E Calvert, Kandice L Dixon, Joseph Piper, Susan L Bennett, Brett A Thibodeaux, Alan D T Barrett, John T Roehrig, Carol D Blair
• Journal: Antiviral research (Antiviral Res) Vol. 131 Pg. 92-9 (07 2016) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 27126613 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antibodies, Neutralizing
• Antibodies, Viral
• Receptors, Interferon
• Viral Envelope Proteins
• Yellow Fever Vaccine

Topics

• Animals
• Antibodies, Monoclonal, Humanized (immunology, therapeutic use)
• Antibodies, Neutralizing (immunology, therapeutic use)
• Antibodies, Viral (immunology, therapeutic use)
• Disease Models, Animal
• Humans
• Immunization, Passive
• Mice
• Neutralization Tests
• Receptors, Interferon (deficiency, genetics)
• Viral Envelope Proteins (immunology, metabolism)
• Yellow Fever (immunology, prevention & control, therapy)
• Yellow Fever Vaccine (adverse effects, immunology)
• Yellow fever virus (immunology)