The purpose is to evaluate efficacy and safety of therapeutic hepatitis B virus (HBV) vaccine (mimogen-based)) Joint entecavir treatment in chronic hepatitis B patients.

Eligible subjects are enrolled and assigned into 2 groups randomly with a 1:1 ratio：

1. Therapeutic HBV vaccine Joint Entecavir group：Inject εPA-44 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48 + Oral intake entecavir 0.5mg per day ；
2. Empty liposome Joint Entecavir group：Inject empty liposome at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48 + Oral intake entecavir 0.5mg per day.

The study cycle consists of screening and enrollment period (week -4～0), treatment and follow-up period (week 0-96).

Inclusion Criteria:

1. Aged 18-65 years, male or female;

2. Conforming to diagnosis standard of chronic hepatitis B according to " 2005 Guideline for Prevention and Treatment of Hepatitis B " , (with positive HBsAg for more than 6 months), never have systemic treatment of anti-HBV viral ,and

   • HBV-DNA ≥ 1.72×10^4 IU/ml；
   • HBeAg (+), HBeAb (-)；
   • ALT within 2 to 10 times of ULN (upper limits of normal);

3. HLA-A2 positive;

4. Compensatory liver disease having following hematological and biochemical parameters:

   • WBC ≥ 3.5×10^9/L;
   • ANC ≥ 1.5×10^9/L;
   • PLT ≥ 80×10^9/L;
   • Hb ≥ 100g/L;
   • TBil ≤ 1.5 ULN;
   • ALB not lower than low limit of normal value;
   • BUN no more than high limit of normal value;
   • Cr ≤ 1.5 ULN high limit of normal value;
   • PT elongation ≤ 3 sec, APTT in normal value;
   • Fasting blood glucose ≤ 7.0mmol/L;

5. TSH in normal value;

6. AFP test result no more than high limit of normal value;

7. Take effective contraception for subject with child-bearing potential (including females and female partners of males);

8. Understand and sign ICF approved by EC;

9. Willing to comply with the study procedures and complete the study.

Exclusion Criteria:

1. Antibodies of HCV, HDV or HIV is positive;

2. ANA titer > 1:100;

3. Decompensated liver disease (such as gullet and pylorus varicose veins, hepatic encephalopathy);

4. Have the following illness or with severe disease inappropriate to participate in the study in the view of the investigator, in cardiovascular system: instable or significant cardiovascular illness such as angina pectoris, heart attack of myocardial infarction, congestive heart failure, severe hypertension, significant arrhythmia or abnormal ECG etc;

   • Respiratory system: bronchiectasia, bronchial asthma, chronic obstructive pulmonary disease, respiratory failure, etc;
   • Endocrine, metabolism diseases: diabetes mellitus, uncontrolled thyroid diseases, etc;
   • Others: autoimmune disorder, active tuberculosis, malignancies (e.g.: tumor), neuropathic, metal, acute or chronic pancreatitis illness history, etc.

5. Have used anti-HBV drug ( Interferon, Lamivudine, Adefovir Dipivoxil, Entecavir and Telbivudine ) and immunomodulator ( Thymic peptide, etc ) to the administration of study medication;

6. Have allergic diathesis or have suspected allergy to εPA-44;

7. Female in pregnancy, lactation or those who plan to pregnancy during the course of the study;

8. Have history of alcohol abuse (Alcohol consumption for more than 5 years, with daily consumption over 40g for males and over 20g for females) and known drug dependence;

9. Have history of organ transplantation (except corneal transplantation and hair transplantation);

10. Have participated in any other drug clinical investigations within 3 months;

11. Any other factors inappropriate for enroll in the study or study completion in the view of the investigator.