Hepatitis B (HBV)
The life-cycle of HBV is unique. Once a cell becomes infected multiple copies of the viral genome are incorporated in circular form in the nucleus of the infected cells. This so-called cccDNA effects a constant production of new virions and a permanent stimulation of the immune system via massive production of the viral S antigen (HBsAg). This chronic inflammation is the core reason for the development of cirrhosis and liver carcinoma. Therefore, a functional cure of the disease is only possible if the infected liver can get cleared from hepatocytes harboring cccDNA.
The use of vaccines based on the virus S protein as well as the prolonged treatment with nucleotide/nucleoside drugs reduces the symptoms of the disease but does not cure the patients. After withdrawal of these drugs a recurrence of the disease is usually observed.
Viravaxx’s innovative approach for developing a curative vaccine is based on the fact that infected liver cells live significantly shorter than healthy hepatocytes. Therefore, if viral entry to uninfected cells can be inhibited long enough to allow for infected cells to die off by apoptosis, the liver has the chance to regenerate to a healthy state.
The target Viravaxx indentified for the development of its first HBV vaccine (VVX001) is the sodium-taurocholate cotransporting polypeptide (NTCP). This receptor on hepatocytes is used by HBV as a point of entry into the cells. The binding site of HBV to the entry receptor has been mapped to the N-terminal region of PreS. Therefore, the blockade of the PreS-NTCP interaction should provide an efficient inhibition of virus entry.
Viravaxx has already shown that VVX001 is capable of eliciting an immune response focused on the NTCP binding site. Antisera from vaccinated animals and humans are able to block HBV infection in cell culture.
The potential of VVX001 for a sustainable virus load reduction will soon be tested in an exploratory clinical trial in patients with chronic HBV infection.