www.altaweb.it/hepacivac the hcv vaccine: cooperation in the shadow of the pyramids antonella...
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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
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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