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HCV Vaccine

Key facts (World Health Organization, WHO)

  • HCV can cause both acute and chronic hepatitis, which lead to cirrhosis and liver cancer. Each year 399,000 people die from HCV-caused diseases, mostly from cirrhosis and hepatocellular carcinoma.
  • 71 million people live with chronic HCV infection globally. This virus infects 1-2% of the world population with estimated 1.5-2.0 million new infections every year. As reported by the US CDC, new HCV infections have more than tripled from 2011 to 2016
  • There is currently no effective vaccine against HCV.  On May 29, 2019, NIH reported the failed therapeutic (T-cell) vaccine trial.

Envelope Glycoproteins E1 and E2

  • HCV entry into hepatocytes involves CD81, SRB1, CLDN1 and OCLN as the major entry factors
  • Envelope glycoprotein E1/E2 complex is responsible for HCV entry into hepatocytes
  • E2 is the main target of neutralizing antibodies (NAbs) during natural infection

E2 Optimization For Multivalent 1c-SApNP Vaccine Design

Main hypothesis:

The optimized HCV E2 core, with enhanced structural stability, can be displayed on self-assembling protein nanoparticles (1c-SApNP) as vaccine candidates and induce broad and potent neutralizing antibodies (bpNAbs) more effectively than E1E2 or E2 alone.

3 Nanoparticle Platforms & Their EM Images

 

 

The Vaccine Concept

Robust Production in Various Expression Systems

Mouse Immunization: Study Design

 

Longitudinal Analysis of HCV E2-specific Ab Titers

 

Autologous (H77) Neutralization By Serum Antibodies

Cross-neutralization By Serum