TY - JOUR
T1 - Development of antibody therapeutics against flaviviruses
AU - Sun, Haiyan
AU - Chen, Qiang
AU - Lai, Huafang
N1 - Funding Information:
We appreciate the contributions by Junyun He, Ming Yang, Jonathan Hurtado, Collin Jugler, Adrian Esqueda, Sean Madden, Yousif Youhana, Allen Ramollari, and other current and former members of the Chen laboratory for research cited in this review. We also thank Collin Jugler for the critical reading of the manuscript. We appreciate the assistance of Jonathan Hurtado in preparing the figures. Research in the authors’ laboratory was supported in part by National Institute of Health NIH-NIAID grants U01 AI075549 and R21/R33AI101329 to Qiang Chen and a Biodesign Seed Fund.
Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018/1
Y1 - 2018/1
N2 - Recent outbreaks of Zika virus (ZIKV) highlight the urgent need to develop efficacious interventions against flaviviruses, many of which cause devastating epidemics around the world. Monoclonal antibodies (mAb) have been at the forefront of treatment for cancer and a wide array of other diseases due to their specificity and potency. While mammalian cell-produced mAbs have shown promise as therapeutic candidates against several flaviviruses, their eventual approval for human application still faces several challenges including their potential risk of predisposing treated patients to more severe secondary infection by a heterologous flavivirus through antibody-dependent enhancement (ADE). The high cost associated with mAb production in mammalian cell cultures also poses a challenge for the feasible application of these drugs to the developing world where the majority of flavivirus infection occurs. Here, we review the current therapeutic mAb candidates against various flaviviruses including West Nile (WNV), Dengue virus (DENV), and ZIKV. The progress of using plants for developing safer and more economical mAb therapeutics against flaviviruses is discussed within the context of their expression, characterization, downstream processing, neutralization, and in vivo efficacy. The progress of using plant glycoengineering to address ADE, the major impediment of flavivirus therapeutic development, is highlighted. These advancements suggest that plant-based systems are excellent alternatives for addressing the remaining challenges of mAb therapeutic development against flavivirus and may facilitate the eventual commercialization of these drug candidates.
AB - Recent outbreaks of Zika virus (ZIKV) highlight the urgent need to develop efficacious interventions against flaviviruses, many of which cause devastating epidemics around the world. Monoclonal antibodies (mAb) have been at the forefront of treatment for cancer and a wide array of other diseases due to their specificity and potency. While mammalian cell-produced mAbs have shown promise as therapeutic candidates against several flaviviruses, their eventual approval for human application still faces several challenges including their potential risk of predisposing treated patients to more severe secondary infection by a heterologous flavivirus through antibody-dependent enhancement (ADE). The high cost associated with mAb production in mammalian cell cultures also poses a challenge for the feasible application of these drugs to the developing world where the majority of flavivirus infection occurs. Here, we review the current therapeutic mAb candidates against various flaviviruses including West Nile (WNV), Dengue virus (DENV), and ZIKV. The progress of using plants for developing safer and more economical mAb therapeutics against flaviviruses is discussed within the context of their expression, characterization, downstream processing, neutralization, and in vivo efficacy. The progress of using plant glycoengineering to address ADE, the major impediment of flavivirus therapeutic development, is highlighted. These advancements suggest that plant-based systems are excellent alternatives for addressing the remaining challenges of mAb therapeutic development against flavivirus and may facilitate the eventual commercialization of these drug candidates.
KW - Antibody
KW - Antibody-dependent enhancement (ADE)
KW - Dengue virus (DENV)
KW - Flavivirus
KW - Monoclonal antibody (mAb)
KW - Plant-made antibody
KW - Plant-made pharmaceuticals (PMP)
KW - Therapeutics
KW - West Nile virus (WNV)
KW - Zika virus (ZIKV)
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U2 - 10.3390/ijms19010054
DO - 10.3390/ijms19010054
M3 - Review article
C2 - 29295568
AN - SCOPUS:85039044028
SN - 1661-6596
VL - 19
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 1
M1 - 54
ER -