Safety and Efficacy of a Novel Candidate Peptide Vaccine Against HCV Infection in Healthy Volunteers and in Treated (Non-responders/ Responders) Chronic HCV Patients. Clinical Trials Phases I and II

In the present work, we plan to study the safety and efficacy of a peptide vaccine termed Cenv3 ( C for HCV, en for envelop, v for vaccine, 3 for 3 epitopes). The main outlines of the current study include: 1) Examining the safety parameters throughout the vaccination period including acute and chronic reactions if present in a phase 1 clinical study ( i.e. in healthy volunteers). The vaccine will be administered sc at 3 escalating doses in presence and absence of adjuvant. Bioavailability of the vaccine throughout the experiment duration will also be determined. 2) Assessment of the humoral and cellular immune responses towards Cenv3 in healthy volunteers ( higher risk for acquiring HCV infection). 3) Evaluation of the neutralizing capacity of the generated Abs to interfere with intracellular replication of HCV in permissive cell lines

ii) Objective The present proposal aims at:-

1. Examining safety and tolerability towards the candidate HCV peptide vaccine in healthy volunteers.
2. Testing cell mediated immunity via cytotoxic T lymphocyte responses in vaccinated healthy subjects ( CMI).
3. Determining epitope specific B cell response and antibody titers in vaccinated individuals (humoral Immunogenicity).
4. Testing the viral neutralization by antibodies against the vaccine epitopes. (Efficacy).
5. Studying the bioavailability of the peptides in subjects' circulation throughout the vaccination time and 90 days post vaccination.

iii) Study population

Subjects with any cardiovascular problems, asthma, or allergies, should be excluded from the study. Also, any subject who has participated in any experimental medicine clinical trial in the past 3 months will be excluded. Healthy volunteers including subjects from both sexes, 18-55 years of age will be enrolled. All subjects had to fulfill all inclusion criteria as follows: mentally and physically healthy, no clinically relevant pathological findings in any of the investigations of the pre-study examination including blood chemistry ( liver and kidney function tests), differential blood counts, coagulation test, ultrasensitive C-reactive protein levels. Subjects should be able to provide written informed consents. The exclusion criteria included pregnant or breast feeding women, patients with chronic viral-infections (e.g., HBV, HCV, HIV, CMV, HSV), evidence of decompensated liver disease, pre-existing hematuria, or proteinuria, cryoglobulin levels >1% or other immunologically driven diseases, schistosomiasis, acute infectious illness, severe psychiatric disorders, current or past history of malignancy and patients who received treatment with interferon or any investigational therapy for hepatitis during the 3 months prior to study entry.