Development of antibody therapeutics against flaviviruses

Haiyan Sun, Qiang Chen, Huafang Lai

Research output: Contribution to journalReview articlepeer-review

49 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number54
JournalInternational journal of molecular sciences
Volume19
Issue number1
DOIs
StatePublished - Jan 2018

Keywords

  • Antibody
  • Antibody-dependent enhancement (ADE)
  • Dengue virus (DENV)
  • Flavivirus
  • Monoclonal antibody (mAb)
  • Plant-made antibody
  • Plant-made pharmaceuticals (PMP)
  • Therapeutics
  • West Nile virus (WNV)
  • Zika virus (ZIKV)

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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