Hepatitis B Vaccine

The life-cycle of Hepatitis B virus 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’ 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’ vaccine candidate VVX001 targets the sodium-taurocholate co-transporting polypeptide (NTCP) receptor. Hepatitis B virus, more precisely its pre-S protein, uses this receptor as point of entry into cells: Valenta et al, 2020, Quantification, epitope mapping and genotype cross-reactivity of hepatitis B preS-specific antibodies in subjects vaccinated with different dosage regimens of BM32EBioMedicine 59: 102953; https://doi.org/10.1016/j.ebiom.2020.102953.

 

Viravaxx HBV VVX001

VVX001 triggers an immune response which blocks the virus from binding to NTCP, and, thus, efficiently inhibits virus entry. The potential of VVX001 to sustainably reduce virus load is currently being tested in a clinical phase II trial in chronically infected Hepatitis B patients: ClinicalTrials.gov.