Download Open Information Day 2011

The HCV vaccine:
cooperation in the
shadow of the
pyramids
Antonella
Folgori
www.altaweb.it/hepacivac
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
Africa
31.9 million
Prevalence of infection
>10%
2.5%–10%
0.5%–2.5%
No information
World Health Organization 2008
Eastern
Mediterranean
21.3 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)
Europe
8.9 million
Western Pacific
62.2 million
Americas
13.1 million
Southeast Asia
32.3 million
Africa
31.9 million
Prevalence of infection
>10%
2.5%–10%
0.5%–2.5%
No information
Eastern
Mediterranean
21.3 million
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
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
Virus
Target cell
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
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
Recombinant viral vectors
Antigenic
peptide
Antigen encoding
gene
MHC
Immune system
activation (T cells & Abs)
Antigen
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
HCV Vaccine for Prophylaxys and Therapy:
The HEPACIVAC Strategy
Surface antigens
HCV
E1E2
Subunit vaccine
+++ Antibodies
+/- T cells
Genetic vaccine 2
Non Structural antigens
NS
Genetic vaccine 1
+++ T cells
NO GO
Preclinical evaluation in mice and non human primates
Manufacturing in GMP
01
Go to Clinical trials
 Has the effort been successful?
 What next?
06
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
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
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
Acknowledgments: