Unlocking the promise of DNA vaccines

Lead Research Organisation: Imperial College London
Department Name: Infectious Disease

Abstract

Nucleic acid based vaccines are an extremely promising tool to combat pandemics 1. They are cheap, safe and rapidly responsive to novel emerging pathogens. The partner company for this application, Touchlight Genetics, has a GMP ready, completely synthetic DNA platform that is easily scalable. The limitation is that DNA vaccines have underperformed in human clinical trials to date. There are a large number of variables that may limit the efficacy of DNA vaccines and there is an urgent need to perform systematic underpinning research to identify these limiting factors and develop approaches to overcome them in order to develop clinically effective DNA vaccines.

The project will focus on developing a DNA encoded influenza vaccine. This has both commercial value - the sales of seasonal influenza vaccine were approximately $3.1 billion in 2013, and also considerable societal value in the development of vaccines that could prevent pandemic influenza, with flu being the major risk of global pandemics. The Tregoning lab also has well established models of influenza infection 2, that can be used to test the efficacy of any vaccine developed.
The hypothesis of the project is that the immunogenicity of DNA vaccines can be dramatically enhanced, leading to better translation into a clinical product.

The student will work closely with Touchlight Genetics to generate a synthetic DNA influenza vaccine candidate with optimised immunogenicity. In previous work with Touchlight Genetics, we have shown that their linear DNA platform is comparable to plasmid DNA 3, that altering the route of administration alters the type of immune response induced 4 and that the induction of lung resident T cells improves protection against viral infection 5.

The objectives of the project are:
Year 1: Use Touchlight's technology platforms to alter the expression and immunogenicity of DNA vaccines in vivo.
Year 2: Design and test novel influenza DNA vaccines with increased breadth and coverage.
Year 3: Investigate how DNA immunisation can prime the immune system to respond better to other vaccine platforms.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
MR/R015732/1 01/10/2018 30/09/2025
2290727 Studentship MR/R015732/1 01/10/2019 31/08/2023