The life-cycle of HBV is unique. Once liver cells become infected, multiple viral genome copies are incorporated into the cell nucleus. The so-called cccDNA triggers constant production of new virions and permanently stimulates the immune system by ways of massive viral S antigen (HBsAg) production. Subsequent chronic inflammation causes cirrhosis and liver carcinoma.
Vaccines based on virus S protein and treatment with nucleoside drugs reduce the symptoms of the disease, but do not provide a functional cure of Hepatitis B. After withdrawal of these drugs, recurrence of the disease is usually observed.
Viravaxx’s curative vaccine approach bases on the fact that infected liver cells die more rapidly than healthy, uninfected cells. If viral entry to uninfected cells can be inhibited long enough, infected cells will eventually undergo apoptosis and die. Consequently, the liver has the chance to regenerate to a healthy state.
Viravaxx has identified sodium-taurocholate co-transporting polypeptide (NTCP) as target for its vaccine candidate VVX001. This receptor is used by HBV as point of entry into cells. The binding site of HBV to the entry receptor has been mapped to the N-terminal region of PreS.
VVX001 triggers an immune response directed to the NTCP binding site. Blocking of the PreS-NTCP interaction efficiently inhibits virus entry as has been shown in cell culture experiments with antisera from vaccinated animals and humans.
The potential of VVX001 to sustainably reduce virus load is currently being tested in a clinical phase II trial in patients with chronic HBV infection. Source: ClinicalTrials.gov.