Establishing a Novel approach to Plague Vaccine testing - A Feasibility Study of an Attenuated Yersina pestis Vaccine Challenge Model

Summary 

Plague – caused by the bacterium Yersinia pestis – is a historic pandemic disease that still poses a threat today. It remains endemic in several countries across Africa, South America, and Asia, where it can spread from animals to humans. There are concerns about its use in bioterrorism. Despite the need for newer, more effective plague vaccines, generating enough clinical data for their approval is difficult.

We aim to accelerate development of vaccines against Yersinia pestis by creating a human vaccine-challenge study. Although it's unethical to expose healthy people to natural disease-causing bacteria, we propose using weakened vaccine-strain bacteria (from a well-established vaccine called EV76) as a model. This vaccine has been given to millions of people and it has a good safety profile.

Our project aims to lay the groundwork for a proposed future clinical trial, with two packages of work covering public engagement and strain characterisation.

Firstly, we will undertake a programme of public engagement to explore the public attitudes to a proposed challenge study using a weakened version of the plague bacteria. Secondly, we will characterise the EV76 challenge-vaccine, by examining its genetic makeup and how it relates to circulating strains. We will establish partnerships with global collaborators in countries where plague is present, to build a consortium for future clinical trials and surveillance activities.

This project is the first step in evaluating a new model for testing plague vaccines and will help build partnerships for future research.

Project Outcomes

Yersinia pestis is the causative agent of plague – the archetypal bacterial pandemic disease. Plague remains endemic in several countries in Africa, South America, and Asia, posing a high risk of epidemic spread from zoonotic spill-over. There is also a possible threat from use as a bioterrorism weapon. Generating sufficient field data for vaccine licensure is challenging, because outbreaks are unpredictable and the number of cases relatively low. The project funded by BactiVac has enabled the development of the foundations for a human vaccine-challenge study (using an old generation attenuated bacterial strain that has been deployed in some countries as a vaccine) to accelerate development of Yersinia pestis vaccines. Firstly, we were able to explore public attitudes to developing a Yersinia pestis challenge model, which generated key insight points around the overall acceptability and the importance of clear language around giving people an attenuated, non-pathogenic strain of bacteria as part of the study. Secondly, we were able to confirm that the Yersinia pestis bacterial strain we are hoping to use is closely related to currently circulating strains, both in terms of genetic sequence and conservation of key vaccine antigens. Finally, we have been able to bring together a consortium of global experts to work together on developing a Yersinia pestis challenge model.