Landscape of Monoclonal Antibodies Targeting Zika and Dengue: Therapeutic Solutions and Critical Insights for Vaccine Development

Abstract

The unprecedented 2015-2016 Zika outbreak in the Americas sparked global concern and drove the rapid deployment of vaccine and therapeutic countermeasures against this re-emerging pathogen. Alongside vaccine development, a number of potent neutralizing antibodies against Zika and related flaviviruses have been identified in recent years. High-throughput antibody isolation approaches have contributed to a better understanding of the B cell responses elicited following infection and/or vaccination. Structure-based approaches have illuminated species-specific and cross-protective epitopes of therapeutic value. This review will highlight previously described monoclonal antibodies with the best therapeutic potential against ZIKV and related flaviviruses, and discuss their implications for the rational design of better vaccine strategies.

Keywords: Dengue virus; Zika virus; monoclonal antibody; neutralizing antibody; therapeutics; vaccine.

Figure 1

Neutralizing epitopes of Zika virus (ZIKV) and dengue virus (DENV) monoclonal antibodies. Top, Characteristics of prototypical ZIKV and DENV neutralizing antibodies grouped by epitope specificities. Neutralization potency is based on IC50 against ZIKV unless otherwise indicated. IC50 (ng/ml) are indicated as follows: **** (<10 ng/ml); *** (10–50 ng/ml); ** (50–500 ng/ml); * (>500 ng/ml). Bottom, the same neutralizing epitopes mapped onto the ZIKV E dimer. The ZIKV E dimer, PDB 5LBV (25), is shown in ribbon representation with the respective domains of each protomer colored in red (DI), yellow (DII), and blue (DIII) while the fusion loop in DII is highlighted in green. This visual was generated using UCSF Chimera (48).