Prof. Fatma Amer Medical Microbiology and Immunology, ZAGAZIG FACULTY OF Medicine, Egypt President...

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