By Rideeta Raquib ’19

The Zika virus (ZIKV) is a deadly virus transmitted through mosquito bites that at its climax has infected more than 1.5 million people in Brazil in 2015. The virus continues to spread with approximately 200 ZIKV cases reported in the United States this year. In order to combat the epidemic, new ZIKV vaccines have been developed to inactivate the virus. However, these vaccines predisposed people to infection by the Dengue virus (DENV), a viral relative of the ZIKV. Recently, researchers at Arizona State University have developed a plant-based ZIKA vaccine that does not induce DENV infection and has reduced negative side effects. They concocted a virus-like particle (VLP) carrier that is based on the hepatitis B core antigen (HBcag) that expresses the ZIKV E protein domain III (zDIII). The HBcag-zDIII elicited immune responses against multiple ZIKV strains and can be produced, as well as purified, efficiently in large quantities from Nicotiana benthamiana plants. The purification process eliminates any contamination that can interfere with the detection and performance of the complex.

In order to create the vaccine, the researchers initially detected the expression of Hbcag-zDIII by conducting sucrose gradient sedimentation of plant extracts, whereby the plant cells are differentiated by centrifugation based on sucrose content. Then, they performed a SDS-Page to separate purified proteins by weight. The researchers then carried out an ELISA assay that was used to determine the presence of the antigen and they found that 64 percent of HBcag-zDIII was recovered from the plant extracts.

In order to examine how effective the HBcag-zDIII VLPs are, the researchers measured the production of cytokines by splenocytes after in vivo antigen stimulation in mice. Splenocytes are a type of white blood cells and cytokines are proteins released during an immune response. Three different adjuvants were administered along with the VLPs; some were more effective than others in inducing cellular immune responses in the mice.

Overall, the study showed that HBcag-zDIII can be efficiently produced, purified, and showed immunogenic activity against multiple ZIKV strains. These results can pave a way for development of more affordable and potent vaccines to tackle the ZIKV epidemic in many countries.

References:

1. Image aqcuired from: http://www.abc.net.au/radionational/image/4183296-3×2-700×467.jpg
2. Ming Yang, Huafang Lai, Haiyan Sun, Qiang Chen. Virus-like particles that display Zika virus envelope protein domain III induce potent neutralizing immune responses in mice. Scientific Reports, 2017; 7 (1) DOI: 10.1038/s41598-017-08247-9
3. “Zika Virus.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 17 Aug. 2017, http://www.cdc.gov/zika/reporting/2017-case-counts.html.