Project description
Hepatitis B virus (HBV) remains a leading cause of chronic liver disease worldwide, with over 350 million people living with chronic infection and approximately 820,000 deaths annually from cirrhosis and hepatocellular carcinoma. Despite the existence of a safe and effective recombinant vaccine since 1986, vaccination coverage remains critically low in tropical, low- and middle-income countries (LMICs), largely due to the stringent cold-chain requirements of current formulations, which must be maintained between 2–8°C from manufacture to point of delivery.
This proposal presents HePatch, a synthetic biology project aimed at engineering thermostable variants of the hepatitis B surface antigen (HBsAg) and integrating them into dissolvable microneedle patch systems for cold-chain-free vaccine delivery. Our strategy combines rational computational protein engineering, directed evolution, and advanced biomaterial formulation to produce vaccines stable at ambient temperatures exceeding 37–45°C for 28 days or longer.
Our phased methodology involves: (1) computational identification and rational design of thermostabilizing mutations in HBsAg using FoldX, Rosetta, and AlphaFold-based structural predictions; (2) primary validation of thermostability principles using Green Fluorescent Protein (GFP) as a structurally analogous and biosafe model antigen; (3) expression, purification, and biophysical characterization of engineered protein variants; and (4) integration of validated formulations into dissolvable polyvinylpyrrolidone (PVP)-based microneedle arrays capable of ambient-temperature storage with retained antigenicity.
This project directly addresses UN Sustainable Development Goal 3 (Good Health and Well-being) and SDG 10 (Reduced Inequalities) by developing enabling technology for vaccine access in regions where cold-chain infrastructure is absent or unreliable. By eliminating cold-chain dependency, our project has the potential to dramatically increase birth-dose hepatitis B vaccination coverage, particularly in sub-Saharan Africa and Southeast Asia, where HBV transmission rates are highest.
Wiki
Visit the team's wiki-page: To be announced.
Video
To be announced.
The students in the team
Coming soon.