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Multifunctional DNA-based nanostructures targeting follicular dendritic cells for efficacious vaccine responses

Internationalisation Fellowships

What

This project aims to develop a novel and modular vaccine platform that exploits natural pathways of our immune system to elicit a rapid, long-term, and highly effective immune response against any desired pathogen. This methodology utilizes DNA nanotechnology to allow studying combinations of antigens and ligands in a plug-and-play manner, and offers a promising approach for rapid evaluation and development of future vaccines against infectious diseases and as potential cancer treatment.

Why

Globalisation has led to the emergence of novel viral pathogens that cause major pandemics by evading immune recognition. Vaccines are effective in combating pathogens, however conventional vaccines are developed empirically, require repeated administration to prime the immune system, and can take very long time to produce. Therefore, it is of relevance to implement our current knowledge on the molecular mechanisms, following immunisation, in the development of rationally designed vaccines that could rapidly lead to enhanced efficacy and protection against diverse pathogens in animal models. This will result in the establishment of advanced design principles that: 1) considers antigen valency and spatial arrangement on a vaccine platform, 2) exploits the complement system for targeting relevant cells in the lymph nodes, and 3) tailors the immune response towards desired pathogens, and will provide a better understanding of fundamental immunology.

How

We will use DNA origami technology to create structures resembling viruses (DNA-VLP) composed of: 1) antigen against influenza virus, 2) sugar entities that aid the vaccine to target specific cells in our body, and 3) short DNA molecules that boosts the immune response. With the help from specific blood proteins that recognise the sugars, the DNA-VLP vaccines will be rapidly transported to the lymph nodes where they are retained for a long time. In mouse models, this will create an immune response by producing strong antibodies and long-lasting memory against the virus.