A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 inA vitro but does not protect a mouse model from disease

Amanda E. Calvert, Kandice L. Dixon, Joseph Piper, Susan L. Bennett, Brett A. Thibodeaux, Alan Barrett, John T. Roehrig, Carol D. Blair

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 inA 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 inA vitro, it does not have the ability to abrogate disease inA 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.

Original languageEnglish (US)
Pages (from-to)92-99
Number of pages8
JournalAntiviral Research
Volume131
DOIs
StatePublished - Jul 1 2016

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Yellow fever virus
Antibodies, Monoclonal, Humanized
Monoclonal Antibodies
Vaccination
Yellow Fever Vaccine
Interferon Receptors
Viral Envelope Proteins
Therapeutics
Virus Attachment
Infection
Cricetinae
Antiviral Agents
Vaccines
Binding Sites
indium arsenide
Viruses

Keywords

  • Monoclonal antibody therapy
  • Neutralizing antibody
  • Post-vaccinal SAE
  • YFV vaccine

ASJC Scopus subject areas

  • Virology
  • Pharmacology

Cite this

A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 inA vitro but does not protect a mouse model from disease. / Calvert, Amanda E.; Dixon, Kandice L.; Piper, Joseph; Bennett, Susan L.; Thibodeaux, Brett A.; Barrett, Alan; Roehrig, John T.; Blair, Carol D.

In: Antiviral Research, Vol. 131, 01.07.2016, p. 92-99.

Research output: Contribution to journalArticle

Calvert, Amanda E. ; Dixon, Kandice L. ; Piper, Joseph ; Bennett, Susan L. ; Thibodeaux, Brett A. ; Barrett, Alan ; Roehrig, John T. ; Blair, Carol D. / A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 inA vitro but does not protect a mouse model from disease. In: Antiviral Research. 2016 ; Vol. 131. pp. 92-99.
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