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Next generation vaccines to prevent Hepatitis C

Central to the potential success of an HCV vaccine is the ability to confer broad protection against the 7 major circulating HCV genotypes (~30% variation at protein level), comprising over 67 subtypes (~20% variation). Recent studies have shown that broadly neutralising antibodies and a broad and diverse T cell response are requirements of a successful vaccine to prevent HCV. The neutralising antibodies response is predominantly directed towards the viral envelope glycoprotein E2 receptor binding domain. However, viral E2 uses multiple immune evasion mechanisms to restrict the generation of neutralising antibodies including glycan shielding, focussed amino acid sequence evolution in hypervariable regions that allosterically suppress the presentation of antibody epitopes, and immunodominance of epitopes that preferentially generate isolate-specific neutralizing antibodies that drive immune escape and non-neutralising antibodies.

Our approach to HCV vaccine design is based on the rational re-engineering of E2, and CD4+ and CD8+ T cell epitopes informed by structural, biochemical, immunological and functional data.

  • Develop E2 vaccine candidates that focus the immune response on conserved neutralizing antibody epitopes
  • Explore the potential for mRNA vaccine candidates to generate immunity to Hepatitis C in preclinical models. 
  • Progress our lead HCV vaccine candidate into Phase 1 clinical studies to determine safety and immunogenicity in humans.


We use a combination of structural biology, protein engineering and structure function analysis to design new E2 vaccine candidates. Our candidates are tested in preclinical studies to understand if we are generating the desired immune response and we can prevent infection with diverse strains of hepatitis C. We use systems immunology to identify potential correlates of protection of our vaccine candidates from our preclinical studies. Our lead candidate will be used in a Phase I study in humans to determine safety and if we are generating appropriate immune responses in humans prior to initiating a phase 2 efficacy study.

Hepatitis C virus chronically infects more than 50 million people globally and causes approximately 500,000 deaths each year. To address the hepatitis C pandemic, the World Health Organization (WHO) introduced the following targets for 2030: an 80% reduction in new infections. Despite significant progress being made in reducing the number of people living with hepatitis C through the use of direct acting antivirals, it is clear that only a small fraction of countries are on track to reach the WHO elimination targets by 2030. Direct acting antivirals (DAAs) can cure HCV infection in over 95% of people receiving them.

However, DAAs alone are unlikely to achieve HCV elimination because:

  • DAAs are expensive relative to GDP in most countries, restricting their availability, and placing a major impost on healthcare payers.
  • A large number of people have undiagnosed HCV. 3. Improper use of DAAs may cause drug resistance due to HCV’s high mutation rate and high prevalence of pre-existing drug mutations. 4. Even after viral clearance, people remain at risk of contracting HCV if re-exposed, with reinfection rates of 8-12/100 person years.

As a result, a prophylactic vaccine to prevent primary infection and reinfection is urgently needed. A vaccine that prevents infection used along side DAAs will accelerate elimination of HCV and will benefit the community by preventing morbidity and mortality associated with hepatitis C.


Professor Heidi Drummer

Contact Professor Heidi Drummer for more information about this project.



  • mRNA Vic
  • Burnet Institute

Partners +

  • Monash Institute of Pharmaceutical Sciences, Professor Colin Pouton.