Zika virus structural biology and progress in vaccine development

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Zika virus (ZIKV) infection is linked to a significant increase in neonatal microcephaly and central nervous system malformations, particularly in pregnant women.
• ZIKV, a Flavivirus, shares structural similarities with other flaviviruses but exhibits greater thermal stability.
• The ZIKV envelope (E) protein plays a crucial role in viral entry, mediating receptor binding and membrane fusion via its distinct domains (DI, DII, DIII) and fusion loop (FL).

Purpose of the Study:

• To review the structural characteristics of ZIKV relevant to vaccine development.
• To summarize current ZIKV vaccine candidates and strategies.
• To highlight approaches for enhancing immunogenicity and reducing cross-reactivity with related viruses like Dengue virus (DENV).

Main Methods:

• Analysis of high-resolution cryo-electron microscopy structures of ZIKV.
• Review of ongoing research and development of over 50 ZIKV vaccine candidates.
• Investigation of protein engineering strategies for stabilizing ZIKV E:E dimer proteins and developing virus-like particles (VLPs).

Main Results:

• Stabilized ZIKV E:E dimer proteins have been successfully produced through disulfide bond introduction or direct assembly.
• Virus-like particle (VLP) platforms effectively present native E:E dimer antigens.
• Mutations in or near the E protein's fusion loop (FL) show promise in minimizing cross-reactive, antibody-dependent enhancement (ADE)-facilitating antibodies.

Conclusions:

• Over 50 ZIKV vaccine candidates are in development, utilizing diverse platforms like inactivated viruses, viral vectors, nucleic acids, and VLPs.
• Stabilized E:E dimer proteins and VLP-based approaches offer promising strategies for ZIKV vaccine design.
• Future vaccine development should prioritize eliciting potent neutralizing antibodies with reduced cross-reactivity to achieve sterilizing immunity against ZIKV.