RNA vaccine for endemic Plague

Summary

RNA vaccines have come of age through their effective deployment against COVID-19. The aim of this project is to harness this new technology against an old but important infectious threat, Plague. A serious bacterial disease, Plague is endemic in Madagascar, causing seasonal outbreaks, with an exceptionally severe outbreak in 2017/18, with 765 cases resulting in 121 deaths, 16% of those infected. 

Currently there is no approved vaccine, largely due to the high-cost investment in manufacturing conventional protein-based vaccines. We propose a new approach to vaccinate against plague, radically cutting cost and time by using RNA technology for delivery, building on our detailed knowledge of what is required to achieve protective immunity.

Should these studies demonstrate success in animal models, this will provide needed ‘proof of concept” to attract further funding for clinical development and pioneer the use of RNA vaccines for other bacterial threats.

Project Outcomes

The aim of the project is to evaluate an RNA vaccine approach for plague. Plague is a serious bacterial disease, which is endemic in Madagascar, causing seasonal outbreaks, with an exceptionally severe outbreak in 2017/18, with 765 cases resulting in 121 fatalities (case fatality rate 16 %).  Significantly, however, plague is a preventable disease, but there is no approved vaccine, largely due to the cost and time investment in manufacture, clinical trials and licensing of protein-based vaccine approaches for this niche pathogen. This project sought to develop an RNA vaccine against plague, an approach recently proven against COVID-19. We screened a range of RNA vaccine design targeting two key proteins (F and V) of the plague bacteria (Y.pestis). We selected the best vaccine designs for F and V proteins based on the magnitude of antibody responses induced in mice. These were then used to vaccinate mice that were subsequently challenged with Y.pestis. Encouragingly, we observed 85% protection from fatality against a moderate challenge dose and 71% protection against a high dose challenge. These responses were similar to those seen with a control protein-based vaccine. The potential advantage of this approach is that such a vaccine would be faster and cheaper to manufacture. It is hoped that these early encouraging results will support further development of this vaccine and progress towards clinical trials.