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

www.altaweb.it/hepacivac

The HCV vaccine: The HCV vaccine: cooperation in the cooperation in the

shadow of the shadow of the pyramidspyramids

Antonella Antonella Folgori Folgori

2.5%–10%

>10%

0.5%–2.5%

Prevalence of infection

No information

Europe8.9 million

Americas13.1 million

Africa31.9 million

Western Pacific62.2 million

Eastern Mediterranean

21.3 million

Southeast Asia32.3 million

Estimated 170 Million Persons With HCV Infection WorldwideEstimated 170 Million Persons With HCV Infection Worldwide 3-4 million newly infected each year worldwide

World Health Organization 2008

2.5%–10%

>10%

0.5%–2.5%

Prevalence of infection

No information

Europe8.9 million

Americas13.1 million

Africa31.9 million

Western Pacific62.2 million

Eastern Mediterranean

21.3 million

Southeast Asia32.3 million

Egypt has the highest prevalence of HCV infection in the worldEgypt 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)

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• 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 HCV infection and medical needs

A new vaccination approachA 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

Genetic vaccinesGenetic 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

AntigenMHC

Antigenicpeptide

Recombinant viral vectors

Antigen encodinggene

Immune system activation (T cells & Abs)

12 project partners from 7 countries: Belgium, Germany, Italy, the

Netherlands, Poland, UK and Egypt

HCV vaccine: an international team of researchers HCV vaccine: an international team of researchers is rising to the challengeis 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

01

Genetic vaccine 1Subunit 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: HCV Vaccine for Prophylaxys and Therapy: The HEPACIVAC StrategyThe HEPACIVAC Strategy

Surface antigens Non Structural antigens

HCV

Has the effort been successful?Has the effort been successful?

What next?What next?

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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 - IAchievements - I

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 - IIAchievements - 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 Post-HEPACIVAC plans: translate the results into effective effective approaches for prevention and therapy of HCVapproaches for prevention and therapy of HCV

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:Collaborative research required:

Cairo, 2009

Acknowledgments:Acknowledgments: