Study to Evaluate Induction of HBV Virus Neutralizing Antibodies Using VVX001

Inclusion Criteria:

• Cohort 1: hepatits B vaccine naive subjects Seronegative for anti-HBs and anti-HBcantibodies and for HBs Antigen
• Cohort 2: Subjects who failed to develop a protective immune response upon standardvaccination with a licensed hepatitis B vaccine (<10 IU/L anti HbS antibodies)Seronegative for anti-HbS (<10 IU/L) and anti-HBc antibodies and for HbSAg
• Cohort 3: Parameters confirmed at screening during the past 12 months

1. HBeAg negative;
2. HbSAg positive at screening <3000 IU/ml;
3. HBV viral load <2000 IU/ml
4. ALT Levels ≤ULN at screening

• Cohort 4a: Parameters confirmed at screening during the last 12 months

1. HBeAg negative;
2. HbSAg positive <1000 IU/ml
3. HBV DNA not detectable for at least 2 years
4. History of nucleos(t)die Treatment for at least 3 years
5. Willingness to discontinue NUC treatment during study
6. ALT levels ≤ULN at screening

• Cohort 4b: in addition to cohort 4a:

1. willingness to discontinue NUC treatment 6 weeks before entering the Study
2. ALT Levels ≤ULN 6 weeks before entering the study and

• 5x ULN at screening

Exclusion Criteria:

• Pregnant or breast-feeding females, adequate contraception required during thetreatment phase
• History of grass pollen allergy
• Co-infection with HCV, HDV, HIV
• History of auto-immune hepatitis
• Elevated Levels of Alpha-Fetoprotein (AFP) >100 ng/ml
• Documented history of decompensated liver disease (albumin <3.5 g/dl and bilirubin >1.3 mg/dl)
• Autoimmune disorders, transplant recipients, use of immunosuppressive or immunemodulating agents
• Oral corticosteroids of 20 mg/week within the past 4 weeks prior to screening
• History of treatment with PEG-IFN of IFN for at least 1 year prior to screening
• History of evidence or conditions associated with chronic liver disease
• Acute fever at time of enrolment
• History of alcohol abuse
• Planned administration of a vaccine not foreseen by study protocol in the periodstarting 30 days before first product administration and during the entire studyperiod with exception of influenza vaccine
• History of Cancer
• Other severe co-morbid conditions and concurrent medication making the subjectunsuitable for participation
• blood or plasma donation within 1 month of study enrolement and during the course ofthe study
• For all patients with chronic HBV infection:

1. Total bilirubin >2x ULN confirmed by repeat testing within 2 weeks, unlesshistorical documentation of Gilbert's syndrome
2. Documented or suspected hepatocelluar carcinoma
3. Presence of cholangitis, cholecystitis or bile duct obstruction
4. Liver cirrhosis assessed by fibroscan with elastography <9kPa within the previous 12 months and FIB-score <3.2 at study entry