A DNA vaccine against Zika can now be delivered by a simple injection, not a gene gun or electric shock device. The team mixed the DNA with a special formulation that makes it work with an ordinary needle and syringe—solving a problem that has kept DNA vaccines from being widely used. This matters because DNA vaccines are cheap to produce and do not need refrigeration, making them ideal for poor regions hit by disease outbreaks. The vaccine also avoids a dangerous flaw: most dengue and Zika vaccines target the virus’s surface protein, which can cause worse disease if someone later catches a related virus. This vaccine targets a different protein (NS1) to sidestep that risk. If the project succeeds, the team will have a vaccine that protects animals against Zika and can be manufactured in six weeks using synthetic processes, not the usual six-month bacterial method. That speed could transform pandemic response—vaccines could be made directly in affected areas. The same approach could be adapted for other diseases, unlocking a new class of DNA vaccines for global health.
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Our team has developed a DNA vaccine against Zika. Advantages of DNA vaccines are that they can be produced rapidly and cheaply and do not require cold-chain storage. This should make DNA vaccines ideal for responding to future disease outbreaks, especially in poorer regions of the world. However, most DNA vaccines under trial do not work well if delivered using a traditional needle and syringe and instead require an expensive device to deliver the vaccine through the skin (either by 'firing' it, using pressure with a 'gene gun', or using a mild electric shock, electroporation). We have developed an elegant solution to this problem. By mixing the DNA in a special formulation, it can be given by simple injection. We have used Zika as an example disease for which there is no vaccine available yet, which is also true for the related dengue virus. Experience has shown that the usual approach of making a vaccine that causes the body to make antibodies against the envelope protein on the surface of dengue virus may lead to worse disease if a person is later exposed to a similar but not identical virus (so called antibody-dependent enhancement of disease). To avoid this risk, our vaccine contains a non-structural protein (NS1) instead of the envelope protein. We have optimised our vaccine and shown that mice vaccinated with it produce a strong immune response. Our aim in this project is to show we can produce the vaccine in sufficient quantity and at high levels of purity and confirm that the vaccine is able to protect laboratory animals against becoming sick when exposed to Zika virus. A further issue with mass-deployment of DNA vaccines is time to impact, the DNA (as for mRNA vaccines) must be designed, tested and scaled meaning months before use. Here we are championing the use of synthetic-manufacture, over the usual bacterial processes. This cuts time (to 6 weeks versus 6 months) and will allow direct manufacture in affected areas. This could be transformative when deploying vaccines in pandemics. At the end of the project, we will be able to start human clinical trials. Solving the issues that have prevented DNA vaccines from being more widely used could have a transformative impact on pandemic prevention in the developing world and globally. Importantly, this approach allows a new class of DNA vaccines to be employed for many other diseases.
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