prof. fatma amer medical microbiology and immunology, zagazig faculty of medicine, egypt president...
TRANSCRIPT
Prof. Fatma AmerMedical Microbiology and Immunology, ZAGAZIG FACULTY OF Medicine, Egypt
President of ISC/HWGPresident of ArAPUA
In the Era of Direct Acting Antivials; is There a Need for an HCV Vaccine
Global distribution of HCV Treatment of HCV infection The need for an HCV vaccine Challenges for developing an HCV vaccine A successful HCV vaccine Vaccine target Promising outcomes of HCV vaccine
modalities Future vaccination approaches
Overview of the presentation
Global distribution of HCV
BOCTVR
SOC PEG-INF + Ribavirin
the first-generation
direct-acting antivirals
2011
+ SOCFDA, 2013SofospivirSemiprivir
FDAfor type I
FDA, 10/2014Ledipasvir/Sofosbuvir
Once/D, G1
Treatment of HCV infection
The need for an HCV vaccine
Managemant of HCV
infection challenges
Genetic determinants
of host & virus can prevent
100% efficacy
Resistance
Very high cost
Low rate of diagnosis
Reinfection
SOC with many side
effects .
DAAs problems
So, development of safe, effective, and affordable vaccines against HCV remain the best long-term hope for bringing the
global epidemic under control.
Prophylactic vaccine
Current data indicate that vaccine –induced immunity may not prevent
completely HCV infection, but rather prevent persistence of the virus
Acceptable goal. Chronic
persistence main cause of
pathogenesis & development of
serious conditions.
High risk groups
and
Therapeutic vaccine
The need for an HCV vaccine has been emphasized in 2011 when the US Department of Health and Human
Services issued the Viral Hepatitis Action Plan.
Replace/ enhance teatment
Benefits in expenses & logistics if patients treated with 2–3 doses
of vaccine with/without SOC, opposed to months of
combination.
The genetic heterogeneity
which is a hallmark of
HCV as RNA virus
Technical limitations in the study of
HCV
Difficulty of growing the virus in cell culture, a
problem which has been recently
overcome.
Challenges for developing an HCV vaccine
Should address viral heterogeneity, Should cover the various genotypes
and quasispecies of HCV,
Should elicit desired immune response.
A successful HCV vaccine
Desired Immune Response from HCV Vaccine
1. Envelope region:- Hypervariability is an obstacle.
2. Core protein:- Interfere with innate and adaptive immunity - Viral replication inefficiently controlled.
A key question, which HCV antigen a vaccine should target ??
Inducing T-cell responses to NS HCV antigens
- Relatively, genetically conserved, - Known to contain multiple CD4+ & CD8+ T-cell epitopes.
Targeting more than one Ag is most efficient
strategy.
Recent strategies have focused on
Promising Outcomes of a HCV Vaccine Modalities
Terresi et al. (2011) Progress in the development of preventive and therapeutic vaccines for hepatitis C virus. JH; 54(6): 1273-1285.
Promising Outcomes of a HCV Vaccine Modalities
Terresi et al. (2011) Progress in the development of preventive and therapeutic vaccines for hepatitis C virus. JH; 54(6): 1273-1285.
Promising Outcomes of a HCV Vaccine Modalities
Terresi et al. (2011) Progress in the development of preventive and therapeutic vaccines for hepatitis C virus. JH; 54(6): 1273-1285.
Promising Outcomes of a HCV Vaccine Modalities
Terresi et al. (2011) Progress in the development of preventive and therapeutic vaccines for hepatitis C virus. JH; 54(6): 1273-1285.
Promising Outcomes of a HCV Vaccine Modalities
Terresi et al. (2011) Progress in the development of preventive and therapeutic vaccines for hepatitis C virus. JH; 54(6): 1273-1285.
Promising Outcomes of a HCV Vaccine Modalities
Terresi et al. (2011) Progress in the development of preventive and therapeutic vaccines for hepatitis C virus. JH; 54(6): 1273-1285.
Promising Outcomes of a HCV Vaccine Modalities
Terresi et al. (2011) Progress in the development of preventive and therapeutic vaccines for hepatitis C virus. JH; 54(6): 1273-1285.
Promising Outcomes of a HCV Vaccine Modalities
Terresi et al. (2011) Progress in the development of preventive and therapeutic vaccines for hepatitis C virus. JH; 54(6): 1273-1285.
Promising Outcomes of a HCV Vaccine Modalities
Terresi et al. (2011) Progress in the development of preventive and therapeutic vaccines for hepatitis C virus. JH; 54(6): 1273-1285.
DC-Based vaccines against HCV
Human subjects: DC-based vaccine
could work as effective therapy.
Applications for VLPs. Combination modality.
Future vaccination approaches
Chimeric HBV-HCV Vaccine
Beaumont E , et al. Chimeric hepatitis B virus/hepatitis C virus envelope proteins elicit broadly neutralizing antibodies and constitute a potential bivalent prophylactic vaccine. Hepatology.2013 Apr;57(4):1303-13.
Suggested Prime- Boost Vaccination Strategy
T cell Response
Anti-E1 and Anti-E2 Cross-
neutralizing Abs
A Prime Boost Strategy
Adenovirus
Bivalent HBV-HCV
Prophylactic Vaccine
Vaccines with Highly
Protective, Long Lasting Immunity to
HCV and HBV
There have been tremendous advances in the development of antiviral therapy to treat chronic HCV infections. However, there still remains the problem of treating chronically infected persons for whom the use of antiviral drugs is impractical because of cost and logistics. Availability of therapeutic and prophylactic vaccine can provide more cost-effective alternatives.
Conclusions
