1. www.altaweb.it/hepacivac The HCV vaccine: cooperation in the shadow of the pyramids Antonella Folgori

2. 2.5%–10% >10% 0.5%–2.5% Prevalence of infection No information Europe 8.9 million Americas 13.1 million Africa 31.9 million Western Pacific 62.2 million Eastern Mediterranean 21.3 million Southeast Asia 32.3 million Estimated 170 Million Persons With HCV Infection Worldwide  3-4 million newly infected each year worldwide World Health Organization 2008

3. 2.5%–10% >10% 0.5%–2.5% Prevalence of infection No information Europe 8.9 million Americas 13.1 million Africa 31.9 million Western Pacific 62.2 million Eastern Mediterranean 21.3 million Southeast Asia 32.3 million Egypt has the highest prevalence of HCV infection in the world 15% anti-HCV positive among adult rural Nile Delta inhabitants (EDHS, 2009; Strickland 2006; Frank et al, 2000; Abdel-Aziz et al, 2000; Waked et al, 1995)

4. 19 Infection is usually asymptomatic 80% of infected individuals become chronic HCV is a common cause of liver disease and represents a major threat to the health of many people around the world Interferon based treatment is effective in many people but it has extensive side effects and it is very expensive The addition of new antiviral agents will improve virological response rates and decrease the duration of treatment but will likely have further side effects and additional costs Large population of undiagnosed and untreated persons Historically, vaccination is needed to eradicate infectious diseases - not drugs HCV infection and medical needs

5. A new vaccination approach  A classical vaccine triggers the production of antibodies which recognize the surface of the virus  In the case of HCV this structural part changes constantly  The new vaccination approach relies on the generation of «killer» T lymphocytes that reacts to the presence of infectious agents and destroy the infected cells  In the case of HCV T-cell response plays a critical role in viral control in early infection Target cell Virus Cytotoxic T lymphocytes Infected target cell Virus Antibodies

6. Genetic vaccines  The best way to elicit a T cell response is to deliver the gene coding for parts of the infectious agents  The gene is used as a source of antigen and the muscle as a “bioreactor” to produce the corresponding protein Antigen MHC Antigenic peptide Recombinant viral vectors Antigen encoding gene Immune system activation (T cells & Abs)

7.  12 project partners from 7 countries: Belgium, Germany, Italy, the Netherlands, Poland, UK and Egypt HCV vaccine: an international team of researchers is rising to the challenge  Development of a prophylactic HCV vaccine – to eradicate infection  Use the same approach to treat infected patients – to improve on SOC

8. 01 Genetic vaccine 1 Subunit vaccine Preclinical evaluation in mice and non human primates Manufacturing in GMP +++ T cells +++ Antibodies +/- T cells Genetic vaccine 2 NO GO Go to Clinical trials E1E2 NS HCV Vaccine for Prophylaxys and Therapy: The HEPACIVAC Strategy Surface antigens Non Structural antigens HCV

9.  Has the effort been successful?  What next? 06

10.  Preclinical testing of the vaccine: safety, tolerability and strong immunogenicity demonstrated in animal models  Standardization of the procedures for pre-clinical and clinical trials for HCV  Transfer of knowledge (and reagents!) between participant groups in particular from Europe to Egypt  Evaluation of HCV incidence and cell mediated immune responses among Egyptian HCW: a preparedness study for a future Phase II trial of the HCV prophylactic vaccine in Egypt Achievements - I

11.  Two Clinical studies in healthy volunteers for safety, dose and administration regimens optimization – completed: vaccine very safe & highly immunogenic  Three Clinical studies in in chronically infected patients with and without the gold standard therapy – in progress; interim data showed that the vaccine is safe and immunogenic Achievements - II  Phase II efficacy study of the HEPACIVAC vaccine in high risk individuals Established strategic alliance with UCSF and JH in the US who study target populations with high and stable incidence of HCV infection Support from NIH  Clinical studies in Egypt Post-HEPACIVAC plans: translate the results into effective approaches for prevention and therapy of HCV

12.  Tight coordination  Networking  Exchange of experimental data and discussion / teleconference meetings among «working groups»  Supervision of the activities so as to ensure the progression of the project towards the delivery of the objectives  Open discussion during annual meetings Collaborative research required: Cairo, 2009

13. Acknowledgments: