www.altaweb.it/hepacivac

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

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

3. 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) Europe 8.9 million Western Pacific 62.2 million Americas 13.1 million Southeast Asia 32.3 million Eastern Mediterranean 21.3 million Africa 31.9 million Prevalence of infection >10% 2.5%–10% 0.5%–2.5% No information

4. HCV infection and medical needs • 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 19

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 Target cell Virus Antibodies • 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 Virus Infected target cell Cytotoxic T lymphocytes

6. Antigenic peptide Antigen MHC 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 Immune system activation (T cells & Abs) Recombinant viral vectors Antigen encoding gene

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

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

9. Has the effort been successful? • Whatnext? 06

10. Achievements - I • 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

11. Achievements - II • 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 Post-HEPACIVAC plans: translate the results into effective approaches for prevention and therapy of HCV • 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

12. Collaborative research required: • 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 Cairo, 2009

13. Acknowledgments: