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.
Highlights
The Flavivirus genus belongs to the family of Flaviviridae, which consists of more than 70 viruses including insect-specific flaviviruses [1,2,3,4]
Ibalizumab, a monoclonal antibody (mAb) that blocks viral entry into host cells has shown efficacy for patients with drug-resist human immunodeficiency virus (HIV) in a phase 3 human trial [40]. Both in vitro and in vivo studies with HIV Env-specific mAbs such as b12, PGT121, and 10–1074 demonstrated that antibody-dependent cell cytotoxicity (ADCC) activity is an important mechanism of mAbs in treating viral infection, especially those caused by cell-associated HIV [41]
These studies illustrated that mAbs are promising therapeutics in treating infectious diseases that can eliminate pathogen infection through multiple mechanisms including neutralization to block viral attachment and fusion, and antibody-induced effector functions (Figure 1)
Summary
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