2025-26 Project (Groppelli & Ma)

Development of a novel and affordable vaccine for worldwide elimination of hepatitis A virus

SUPERVISORY TEAM

Supervisor

Dr Elisabetta Groppelli at City St George’s
Email: e.groppelli@sgul.ac.uk

Co-Supervisor

Prof Julian Ma at City St George’s
Email: jma@sgul.ac.uk

PROJECT SUMMARY

Project Summary

150 million of Hepatitis A Virus (HAV) infections occur yearly worldwide, with patients suffering debilitating symptoms, and healthcare systems shouldering high disease costs. Vaccines are the most effective preventative measure, but HAV licenced vaccines are too pricey and prone to shortages. Dr Groppelli’s lab spearheads the development of a novel HAV vaccine designed to be affordable and deployed globally. The novel vaccine contains virus-like particles (VLPs) that have identical antigenicity as the virus and that can be generated using recombinant DNA technology. This approach relies on molecular and structural virology, and can deliver the highly complex antigenicity of HAV, currently beyond the reach of other vaccine platforms, like mRNA. After making HAV VLPs using mammalian cells, we now want to assess their production in tobacco plants. Indeed, molecular pharming, pioneered by Prof Ma’s lab, has the strong potential for low-cost high-yield manufacturing of therapeutic biomolecules, including vaccines.

Project Key Words

Vaccine development, hepatitis virus, global health, molecularpharming

MRC LID Themes

  1. Global Health
  2. Infectious Disease
  3. Translational and Implementation Research

Skills

MRC Core Skills

  1. Quantitative skills
  2. Interdisciplinary skills

Skills we expect a student to develop/acquire whilst pursuing this project

1. Laboratory: Molecular virology, Virus-Like- Particle expression, immunoassays 
2. Research: project design and delivery
3. Research data presentation (written and oral)
4. Engagement with the Global Health community

Routes

Which route/s are available with this project?

  • 1+4 = Yes
  • +4 = Yes

Possible Master’s programme options identified by supervisory team for 1+4 applicants:

  • City St George’s – MRes Biomedical Science – Infection and Immunity

Full-time/Part-time Study

Is this project available for full-time study? Yes
Is this project available for part-time study? No

Location & Travel

Students funded through MRC LID are expected to work on site at their primary institution, meeting – at the minimum – the institutional research degree regulations and expectations. Students may also be required to travel for conferences (up to 3 over the duration of the studentship), and for any required training (for research degree study). Other travel expectations and opportunities highlighted by the supervisory team are noted below.

Primary location for duration of this research degree: City St George’s, London

Travel requirements for this project: None

Eligibility/Requirements

Particular prior educational requirements for a student undertaking this project

  • Minimum City St George’s institutional eligibility criteria for doctoral study.
  • MSc/MRes in a relevant discipline would be advantageous (Infection; Immunity; Protein Expression)

Other useful information

  • Potential Industrial CASE (iCASE) conversion? = No

PROJECT IN MORE DETAIL

Scientific description of this research project

Every year over 150 million hepatitis A virus (HAV) infections occur worldwide, and the burden of disease is strongly felt at both individual and healthcare system levels. Hospitalisation is required for 40-60% of adults, and ~20% of patients experience a prolonged and relapsed course that can last 6 months. In 2016-18 in the UK, the cost of a single outbreak that affected 800 adults was more than £1,500,000. On average worldwide, infections have been calculated to cost $6,382 for adults (7.5 days hospitalisation) and $1,857 for paediatric patients (3.5 days hospitalisation). 

The WHO Global Health Sector Strategies 2022-2030 promote the end of epidemics of viral hepatitis. This ambitious goal reflects the crucial standing of viral hepatitis amongst global health challenges and relies on the right tools, including vaccines, to be developed and deployed. Indeed, although inactivated vaccines for HAV have been available since the mid 1990s and WHO recommends routine HAV vaccination, their use is severely limited by high price and low availability. The limitations of the licenced inactivated vaccines stem from their reliance on virus culture, which is slow and of poor yield, and the need to use long chemical inactivation to generate a safe product.  

To generate an affordable HAV vaccine that can be deployed globally, Dr Groppelli’s laboratory has developed a novel HAV vaccine based on virus-like particles (VLPs) obtained with recombinant DNA technology. As proof of principle, HAV-VLPs were generated in mammalian cells, the natural host of the virus. Now, in collaboration with Prof Ma, we aim to generate HAV-VLPs in tobacco plants (N. benthamiana), as they offer a safe and economical option to support low-cost and high-yield vaccine production and, ultimately, global deployment.

Project objectives
1.1 Optimisation of HAV-VLP in N. benthamiana and refinement of the molecular design
1.2 Assessment of VLP antigenicity

Techniques
1. Molecular biology: cloning; PCR; sequencing
2. Growth of N. benthamiana, protein expression (Agrobacterium infiltration)
3. HAV VLPs purification and characterisation (density gradients; Western Blotting; ELISA; Cryo-EM, in collaboration with Mike Strauss, McGill University, Canada)

Confirmed availability of specialist materials
The project stems from work led by Dr Elisabetta Groppelli with funding from the Medical Research Foundation. Reagents are available both commercially and from the research community.

Potential risks and their mitigation
Because HAV is a mammalian virus, viral protein expression and assembly in non-mammalian systems (i.e. plants) need careful consideration and monitoring. However, precedents of VLPs generation in non-mammalian systems for other members of the Picornaviridae have been published, therefore validating and supporting  our approach. Examples include poliovirus, for which a VLP-based vaccine is currently undergoing clinical trial in Australia, and in-development VLP-vaccines candidates for Enterovirus A71, Enterovirus D68 and Coxsackieviruses.

More broadly, successful VLPs-based vaccines are currently licenced for papillomaviruses (Cervarix, GSK; Gardasil, MSD).

Further reading

Relevant preprints and/or open access articles:
(DOI = Digital Object Identifier)

Additional information from the supervisory team

The supervisory team has provided a recording for prospective applicants who are interested in their project. This recording should be watched before any discussions begin with the supervisory team.

Groppelli-Ma recording

MRC LID LINKS

Comments are closed.