HBV Vaccine Development

HBV Vaccine Development

Hepatitis B is a global public health problem caused by the hepatitis B virus (HBV), resulting in severe morbidity and mortality. HBV infection of the liver can cause chronic liver disease, including cirrhosis and hepatocellular carcinoma. Symptoms of HBV infection include extreme fatigue, abdominal pain, nausea and jaundice.

Overview of HBV

HBV is an enveloped DNA virus belonging to the family Hepadnaviridae that causes severe liver disease, including cirrhosis and hepatocellular carcinoma. The HBV genome is approximately 3.2 kb in size and contains four partially overlapping open reading frames (ORFs), of which the Pre-S/S ORFs encode overlapping large (L), medium (M) and small (S) envelope glycoproteins, collectively referred to as HBV surface antigens (HBsAg). These proteins share a common S domain, which is the main epitope that triggers the body to produce neutralizing antibodies against the virus.

A simplified figure of the HBV particle and surface antigens. (Pattyn J, et al., 2021)

HBV Vaccine

The best treatments for HBV disease are nucleoside analogs and interferons, which inhibit the virus to stop the disease from progressing. Because there is currently no available treatment to cure HBV infection, vaccination is the most cost-effective way to control the spread of HBV infection. The HBV vaccine has been one of the most successful and groundbreaking vaccines produced in modern times. While the HBV vaccine has been one of the most successful and pioneering vaccines produced in modern times, HBV vaccination also presents challenges.

Challenges of HBV Vaccination

• The incidence of vaccine non-responders is 5-10% due to the presence of genetic resistance, severe liver and kidney disease, or immunosuppression.
• Most vaccinated people do not produce enough levels of antibodies to provide them protection.
• The emergence and transmission of resistant HBV escape mutants induced by the vaccines themselves.
• The absence of efficacious therapy for chronic HBV patients.

Therefore, new and effective HBV vaccines are needed to enhance seroprotecting in non- or low-responders and provide therapeutic immunization for chronic HBV patients.

HBV VLP Vaccine

HBV VLPs vaccines can be developed through various platforms. For example, HBV S antigen (S-HBsAg) is successfully expressed in yeast and assembled into VLPs, which can be used as HBV VLPs vaccines with safety and efficacy. However, the development of HBV VLPs vaccine still needs to be suitable for oral, low-cost and parenteral, so the plant platform to construct HBV VLPs vaccine that can be orally is very important. In addition, oral vaccines provide additional protection through mucosal immunity. Plant platforms such as L. sativa, carrot, potato, and corn can all be used to develop vaccines for HBV VLPs.

Expression of the HBV-S/preS1 chimera in L. sativa (Dobrica MO, et al., 2018)

How We Can Help

CD BioSciences has the expertise to help our clients produce vaccines through the application of VLPs built on plant platforms (including general VLPs from the N. benthamiana platform and VLPs from the L. sativa platform that can be taken orally). As experts in building VLPs from plant platforms, CD BioSciences uses its expertise to help our clients develop HBV vaccines. Please contact us if you are interested.

References

1. Pattyn J.; et al., Hepatitis B Vaccines. J Infect Dis. 2021, 224:343-352.
2. Dobrica MO.; et al., Oral administration of a chimeric Hepatitis B Virus S/preS1 antigen produced in lettuce triggers infection neutralizing antibodies in mice. Vaccines. 2018, 36:5789-5795.