Hepatitis B & D
Background
Hepatitis B (HBV) is a chronic viral infection of the liver that progresses to cirrhosis and liver cancer. The virus integrates into the genome and forms a stable replicative intermediate, cccDNA (i.e. covalently closed circular DNA) that prevent antiviral therapies from clearing the infection.
Hepatitis D (HDV), also known as hepatitis delta virus, requires the surface antigen of HBV in order to generate infectious viral particles. HDV can only productively infect subjects already infected with HBV (i.e. superinfection) or through co-ingection with HBV and HDV. Superinfection with HDV leads to much more rapid progression to cirrhosis and cancer.
Vaccine Objective
The objective of our vaccine is to neutralize the circulating virus and clear infected cells by activating both neutralizing antibodies and T cells to HBV and HDV and thereby limiting the spread of the infection and eliminating HBV and HDV infected cells.
Vaccine Design
The design of our vaccine targets the essential components of both viruses and direct the immune system to target the essential region of the surface antigen found on both HBV and HDV (i.e. PreS1). The PreS1 contains the receptor binding activity of the surface antigen, and is therefore essential for viral entry into liver cells. Antibodies targeting PreS1 are known to neutralize HBV and HDV, and can protect HBV carriers against HDV infection. PreS1-specific B cells take up HBV and HDV particles, process and present to activate T cells.
The vaccine design also direct the immune system to target the HDV large antigen (LAg), which represents the whole HDV proteome (i.e. all HDV epitopes are therefore included). The inclusion of HDV LAg directs T-cell responses to HBV/HDV co-infected cell alongside the PreS1 response. Thus, this approach will bypass immune tolerance in chronic HBV mono-infection.