Abstract
In this study, we described the generation and immunogenicity of the Zika Virus (ZIKV) envelope protein (E) domain III (DIII) as a protein subunit vaccine candidate. ZIKV EDIII (zEDIII) was rapidly produced in E. coli in inclusion bodies. ZIKV EDIII was solubilized, refolded and purified to >95% homogeneity with a one-step Ni2+ affinity chromatography process. Further analysis revealed that zEDIII was refolded properly and demonstrated specific binding to an anti-zEDIII monoclonal antibody that recognizes a zEDIII conformational epitope. Subcutaneous immunization of mice with 25 and 50 μg of zEDIII was performed over a period of 11 weeks. zEDIII evoked ZIKV-specific and neutralizing antibody response with titers that exceed the threshold that correlates with protective immunity against ZIKV. The antigen-specific IgG isotypes were predominantly IgG1 and splenocyte cultures from immunized mice secreted IFN-gamma, IL-4 and IL-6. Notably, zEDIII-elicited antibodies did not enhance the infection of dengue virus in Fc gamma receptor (FcγR)-expressing cells. This study provided a proof of principle for the further development of recombinant protein-based subunit vaccines against ZIKV.
Original language | English (US) |
---|---|
Pages (from-to) | 4287-4294 |
Number of pages | 8 |
Journal | Vaccine |
Volume | 35 |
Issue number | 33 |
DOIs | |
State | Published - Jul 24 2017 |
Keywords
- Antibody-dependent enhancement (ADE)
- Antigen
- Domain III (DIII)
- Envelope protein
- Neutralizing immunity
- Vaccine
- Zika virus
ASJC Scopus subject areas
- Molecular Medicine
- General Immunology and Microbiology
- General Veterinary
- Public Health, Environmental and Occupational Health
- Infectious Diseases