Four young scientists at AGTRU leverage vaccine science and gene therapy advances for novel treatment and prevention of hepatitis B.
The students' projects at the Antiviral Gene Therapy Research Unit (AGTRU) address hepatitis B virus (HBV) at different stages, from strengthening protection against infection to targeting it once it has become chronic.
As World Hepatitis Day is marked on 28 July, these projects show why HBV must be tackled at every stage, from preventing infection to disabling the virus once it has entered liver cells. This work is most urgent for babies and young children, and in high-burden regions such as Africa.
In 2024, around 240 million people were living with chronic HBV, while 1.1 million died from related cirrhosis and liver cancer. Africa accounted for 68% of new chronic infections.
The virus is particularly dangerous when acquired in infancy or early childhood because babies and young children are far less likely than adults to clear it. HBV infection may remain silent for years while continuing to damage the liver, eventually causing fibrosis, cirrhosis, liver failure and liver cancer.
South Africa incorporated the highly effective hepatitis B vaccine into its childhood immunisation programme in 1995. However, coverage gaps remain, while around 5–10% of vaccinated people do not produce a sufficient protective antibody response.
AGTRU PhD student Nazia Samudh is developing an HBV vaccine using self-amplifying RNA, one of the emerging generation of RNA vaccine platforms.
Like conventional mRNA, it gives cells temporary instructions to produce a harmless viral antigen that trains the immune system. Self-amplifying RNA can briefly make additional copies of that message inside the cell. This results in more antigen being produced from a relatively lower vaccine dose.
Because more antigen may be produced from a smaller starting dose, the platform could reduce the amount of RNA needed and, potentially, the cost of vaccination.“Some of our main goals are to address non-responsiveness to current HBV vaccines and investigate whether we can reduce the number of doses required,” says Samudh.
Currently, three doses are required, and Samudh aims to elicit sufficient protection with just two doses.Fewer clinic visits could make vaccination easier in communities where distance, cost and inconsistent access to healthcare make it difficult to complete a multi-dose schedule.
PhD student Keila Neves is testing an adenoviral-vector vaccine followed by an mRNA booster.
“It’s not just a vaccine candidate; it’s an entire regimen,” says Neves.
Samudh and Neves are also testing vaccine candidates that present more of HBV’s outer surface to the immune system. Existing vaccines mainly use the small hepatitis B surface antigen; their candidates incorporate additional regions from the virus’s larger surface proteins, potentially stimulating a broader immune response.
The candidates are designed around HBV subgenotype A1, which predominates in southern Africa and is associated with an increased risk of liver cancer.
AGTRU Master’s student Pieter Jonker is developing a potential treatment for people already living with chronic HBV.
Once HBV has infected a liver cell, it produces messenger RNA carrying the instructions needed to make viral proteins and new virus particles. Jonker is developing microRNA mimics that recognise and bind to these viral messages.
By prompting the cell to destroy the messenger RNA or preventing it from being read, the treatment could reduce viral protein production and suppress replication.
“We are generating a mimic of this microRNA that will bind to the virus’s messenger RNA, essentially stopping it from making more viruses,” he explains.
AGTRU PhD student Tasneem Farhad is investigating whether CRISPR-Cas9 gene editing can recognise and disable persistent HBV DNA in liver cells. A modified adenoviral vector would deliver the gene-editing machinery to its target.
She is also developing a three-dimensional model of chronic HBV infection. Ordinary mice do not naturally reproduce human HBV infection well, making it difficult to test potential treatments.
“The idea is to grow liver cells as a ‘mini liver’, infect them with hepatitis B and model what the infection looks like in a human,” says Farhad.
Such models could provide a better bridge between conventional cell experiments and later-stage studies.
-University of the Witwatersran