Scientists have short memories! Until 2020, the front running nucleic acid vaccine platform was DNA – it was perceived to be more stable, easier to work with, cheaper. The number of clinical trials and research spend on DNA vaccines far outweighed RNA vaccines. Then COVID came along and upturned everything. The success of the clinical trials and then the vaccine rollout ensured that RNA vaccines became a cause celebre, with much if not all of the vaccinology field switching platforms. At least out of curiosity.
However, there is still some mileage in DNA vaccines, especially around scale up and manufacture. The problem had always been that they were poorly immunogenic, especially in humans and large animals. However, some of the technology that has been useful for RNA vaccine delivery, particularly the way in which they are formulated might assist in DNA delivery.
In our latest paper LNP-formulated dbDNA vaccines elicit durable humoral and cellular immunity with distinct kinetics to mRNA in non-human primates we explored the impact of formulation. We were working with a company called Touchlight Genetics – with whom we have collaborated for over 15 years. Touchlight have an approach for manufacturing DNA without the need for bacteria. This is advantageous because of the speed – you can go from sequence to material incredibly rapidly – vital in a pandemic.
In the study we compared a range of methods to deliver DNA vaccines. Initially we looked at the use of microneedles and a technique called electroporation, where an electric current is applied to the vaccine site which helps uptake. These worked in pigs – which are a good model of human immune response, but were maybe not as practical for use in people. So we moved to different LNP formulations to optimise which would work best with DNA. Whilst broadly similar to those used for RNA, there were some differences, relating to how the vaccine material is delivered and where it needs to get to in the cell. We compared RNA and DNA vaccines head to head, and saw an equivalent immune response, this is important as previously RNA vaccines have outperformed DNA vaccines. We then moved into larger animal models and observed that whilst the two vaccines induced equivalent antibody responses, the DNA vaccine lead to greater and sustained T cell responses.
All of which suggests there is still life in DNA vaccines and that ongoing exploration would be beneficial. The main lesson from the COVID vaccine race was that having several shots on goal is much better than banking on a single approach.