Patient description: A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.

Clinical trial eligibility criteria: eligible ages (years): 18.0-65.0,  Hepatitis C Part I and Part II: 1. Informed consent obtained and signed; 2. Male or female patients, age 18-65 years old (inclusive) 3. Female patients will be menopausal for at least 12 months, surgically sterile or agree not to become pregnant from the time of study enrollment until at least 28 days after the administration of vaccine or placebo. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized. If the volunteer is female, of childbearing potential, and sexually active, she agrees to use acceptable contraception. (Acceptable contraception methods are restricted to effective intrauterine devices (IUDs) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination and for the entire study period post-vaccination). Note: A woman is eligible if she is monogamous with a vasectomized male or abstinent, without the additional need for hormonal or barrier birth control methods upon review of a reproductive history. 4. With chronic hepatitis C evidenced by HCV RNA detectable in blood, and A liver biopsy compatible with chronic hepatitis C; 5. Infected with HCV genotype 1; 6. Non-cirrhotic patients, i.e. liver biopsy available within one year prior to baseline, excluding stage 4 fibrosis; otherwise, if no liver biopsy of less than one year is available, it will be performed at baseline; 7. Patients participating in Part I will be non-responder patients: patients having received at least 3 months of pegylated IFN-alpha (IFN-alpha) plus ribavirin, with currently detectable HCV RNA (whether or not they reach, Early Virologic Response (EVR, defined as a reduction of HCV RNA by at least 2 logs from baseline or negative at 12 weeks) and/or SVR) with > 6 months between the end of PEG IFN-alpha treatment and the first TG4040 injection Part IIa will be either non-responder or relapser patients. Part IIb will be treatment-naïve patients: patients who have never received IFN-based treatment 8. Patients must have compensated liver disease, defined through use of the Child-Pugh scoring system with Features of low serum albumin, prolonged prothrombin time, raised bilirubin, ascites and hepatic encephalopathy are scored and patients assigned to Child-Pugh class A, B or C, the later two being decompensated. Only patients with compensated liver disease will be enrolled No history of ascites, hepatic encephalopathy or bleeding from esophageal varices laboratory tests values Serum bilirubin and international normalized ratio (INR) values <1.2 (except in patients with Gilbert syndrome where serum bilirubin may be as high as 3.0 mg/dL) Serum alanine aminotransferase (ALT) < 5 fold the upper limits of normal (ULN) and Other laboratory parameters of grade 0 or 1 (CTC criteria)  Part I and Part II: 1. Co-infection with HBV (indicated by the presence of hepatitis B surface antigen (HBsAg) in serum) or HIV (anti-HIV in serum); patients with HIV positive sexual partner (by history) will not be included; 2. Current HCV therapies through out the trial period 3. Current alcohol abuse or drug addiction that in the opinion of the investigator may interfere with the subject's ability to comply with trial procedures. 4. History of immunodeficiency 5. Known or suspected impairment of immunologic function including moderate to severe kidney impairment 6. Malignancy within the last 5 years, not including squamous cell skin cancer or basal cell skin cancer unless at the vaccination site or history of skin cancer at the vaccination site 7. Significant cardiac disease, evidenced by History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, chest pain or shortness of breath on activity, or other heart conditions under the care of a physician Baseline ECG showing clinically significant abnormalities (e.g., all kinds of advanced atrioventricular block or intraventricular block with QRS >120msec, QTc >460 msec, or frequent premature atrial contractions, atrial fibrillation or other atrial arrhythmias, > ventricular couplets or ST-T wave abnormalities diagnostic of myocardial ischemia or prior myocardial infarction. EKGs will be interpreted by an identified cardiologist at Saint Louis University prior to enrollment Baseline echocardiogram showing clinically significant abnormalities including valvular disease or contractile dysfunction Ten percent or greater risk of developing a myocardial infarction or coronary death within the next 10 years using the National Cholesterol Education Program's risk assessment tool (http://hin.nhlbi.nih.gov/atpiii/calculator.asp) NOTE: This criterion applies only to subjects 20 years of age and older AND only if at least one of the following apply: A) have smoked a cigarette in the past month, and/or B) have hypertension (defined as systolic blood pressure >140 mm Hg) or are on antihypertensive medication, and/or C) have a family history of coronary heart disease in male first-degree relative (father or brother) < 55 years of age or a female first-degree relative (mother or sister) < 65 years of age. 8. Current use of immunosuppressive medication; Corticosteroid nasal sprays, Inhaled steroids for asthma and/or topical steroids are permissible. Persons taking short courses of oral steroids for conditions such as poison ivy will need to wait a period of 2 weeks after completion of the steroids to begin vaccination. 9. History of any one of the following Suicide attempt or hospitalization for depression within the past five years Any current (within 6 months) severe or poorly-controlled psychiatric disorder (e.g., depression, schizophrenia, bipolar illness, obsessive-compulsive disorder, severe anxiety, personality disorder) The following patients must be excluded unless they are assessed and followed by a psychiatrist or other mental health professional who pre-approves their study participation Patients who have had a suicide attempt and/or hospitalization for depression more than 5 years ago Patients who have had a severe or poorly-controlled psychiatric disorder (e.g., depression, schizophrenia, bipolar illness, obsessive-compulsive disorder, severe anxiety, personality disorder) more than 6 months ago but less than 5 years ago. 10. Receipt of any inactivated vaccine 14 days prior to vaccination or for the duration of the study 11. Receipt of any live attenuated vaccine within 30 days prior to vaccination or for the duration of the study 12. Receipt of any MVA vaccine in the last five years 13. Use of any experimental agent within 30 days prior to vaccination or for the duration of the study 14. Receipt of blood products or immunoglobulin within six months prior to vaccination 15. Donation of a unit of blood within 56 days prior to vaccination or for the duration of the study following the first vaccination 16. Acute febrile illness (>100.5 degrees F) on the day of vaccination 17. Pregnant or lactating women 18. Any condition that, in the opinion of the investigator, might interfere with study objectives 19. Known allergy to MVA vaccine 20. Receipt of antiviral drugs such as alpha interferon or ribavirin 21. Other laboratory parameters of grade 2 or more 22. Study personnel engaged in the blinding of this study