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 language | English (US) |
|---|---|
| Pages (from-to) | 92-99 |
| Number of pages | 8 |
| Journal | Antiviral Research |
| Volume | 131 |
| DOIs | |
| State | Published - Jul 1 2016 |
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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 journal › Article
}
TY - JOUR
T1 - A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 inA vitro but does not protect a mouse model from disease
AU - Calvert, Amanda E.
AU - Dixon, Kandice L.
AU - Piper, Joseph
AU - Bennett, Susan L.
AU - Thibodeaux, Brett A.
AU - Barrett, Alan
AU - Roehrig, John T.
AU - Blair, Carol D.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
KW - Monoclonal antibody therapy
KW - Neutralizing antibody
KW - Post-vaccinal SAE
KW - YFV vaccine
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UR - http://www.scopus.com/inward/citedby.url?scp=84966350057&partnerID=8YFLogxK
U2 - 10.1016/j.antiviral.2016.04.013
DO - 10.1016/j.antiviral.2016.04.013
M3 - Article
VL - 131
SP - 92
EP - 99
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
ER -