Principal Investigator: Prof John Edmunds OBE.

Co-investigators: Prof Christl Donnelly CBE FMedSci FRS, Prof Neil Ferguson OBE FMedSci, Prof Nicholas Grassly, Prof Matt Keeling, Prof Peter Horby FRCP FFPH, Dr Michael Tildesley, Prof Deborah Watson-Jones and Dr Conall Watson FFPH.



Control of many deadly diseases, such as Marburg, plague and Lassa is hampered by the lack of licensed vaccines that can be used for emergency response and preventative programmes. To be licensed, vaccines must typically be shown to be safe and effective. Safety can be tested in many settings, but effectiveness can only be tested during an outbreak. This presents many challenges. Clinical trial regulations are written for testing medicines in elite hospitals, not vaccines in epidemics. Outbreaks occur sporadically and unpredictably, and when they do, the immediate public health priority is to stop spread. Research is a lower priority and the outbreak may come to an end before the vaccine can be shown to work. The only Ebola vaccine trial to demonstrate efficacy in West Africa was the novel ring vaccination trial, which accounted for the changing epidemiology of the outbreak and aligned with other public health response efforts (this trial was designed by lead and co-applicants of this proposal).


Vaccine trials against these diseases must be carefully designed to fit the epidemiology, maximising the chance that it can detect how well the vaccine works. Similarly, if a licenced vaccine is available (as may soon be the case for Ebola), then it is often not clear how best to use it. Many of the target diseases are rare and the cost of population mass-vaccination for prevention would be prohibitive. Instead, vaccines are more likely to be targeted at either high risk groups (such as healthcare workers) or be used during an outbreak to limit its spread. However, the logistical challenge of organising a vaccination campaign during an ongoing outbreak is formidable and if campaigns are not well planned and implemented many people will be affected before vaccines can be delivered. There is a need for a way to address these options before trialling them in real life and computer simulations of epidemics provides this framework.


Project Aims and Objectives

The overall aim of VEEPED is to accelerate and streamline the testing of vaccines against a number of pathogens of outbreak potential by providing a rigorous rationale and evidence base for particular trial designs and regulatory pathways. The same evidence combined with results of robust vaccine trials will inform the design of efficient vaccination programmes that will curb the impact of these high-threat epidemic diseases.

Objective 1: Develop flexible data-driven modelling frameworks that can reproduce key transmission dynamics of each priority pathogen in different settings.

Objective 2: Rigorously evaluate trial designs (or post-licensure studies where necessary) using the modelling frameworks for simulation of outbreaks and trials.

Objective 3: Characterise optimal vaccination deployment strategies through simulation.



Project Methods

VEEPED will review and analyse the pattern of outbreaks for a number of highly pathogenic infectious diseases, build computer models to simulate how they may spread in communities, and use these models to design vaccine trials that have the best possible chance of success and efficient vaccination programmes that are likely to reduce the impact of these deadly diseases. Figure 1 indicates some disease archetypes that will be considered in the project. The VEEPED consortium will work with a range of partners to ensure that the results of this project will feed into decision-making about new vaccine development against these deadly diseases.

                                      Figure 1. Total case numbers in prior epidemics and transmission routes of priority diseases.



Public Involvement

A critical question in vaccine trial planning is the acceptability of proposed research to potential participants. Determining if epidemic research can be randomised and the form this should take, such as randomising individual participants or whole communities as clusters, is also important to trial feasibility. Working with social science colleagues, VEEPED will interview potential host communities to inform trial design discussions. This public involvement will also help understand other factors that may affect trial feasibility, such as institutional trust, methods of consent and aligning trial communications with local expectations and values.




The VEEPED Consortium and Partners

This proposal brings together the UK-based world leaders on strategic vaccine policy, epidemic modelling, frontline communicable disease control and vaccine trial design against emerging infectious diseases (see table 1 for lead areas). The VEEPED consortium works closely with the World Health Organization (WHO) on vaccine development and outbreak response modelling, with several members on WHO R&D Blueprint vaccine trial working groups. VEEPED also works in partnership with the Coalition for Epidemic Preparedness Innovation (CEPI), as well as networks of research and public health partners around the world.

VEEPED is funded until March 2021 through by the National Institute of Health Research (NIHR) on behalf of the government-backed UK Vaccine Network.  The VEEPED team have close working relationships with NIHR Epidemiology for Vaccinology sister projects including as co-investigators and cross-membership of scientific advisory boards:

  • AViD: Anthropology of Vaccine Deployment (PI: Dr Shelley Lees, LSHTM). AViD examines drivers of vaccine acceptability around epidemic diseases. AViD are key partners of VEEPED on public engagement around vaccine research in outbreak risk settings.

  • ADAGIO: Adaptive Design And Genomics In Outbreaks (PI: Prof Ben Cooper, Oxford), which investigates the application of adaptive clinical trial methods and pathogen sequencing to vaccine efficacy trials. This might help make trials smaller and easier to complete in epidemics.

  • EDK: Emergency and Epidemics Data Kit (PI:  Dr Chrissy Roberts, LSHTM). Timely vaccination in epidemics can be hampered by slow systems for data capture. EDK develops epidemic and trial data collection tools in OpenDataKit for Android tablet computers, allowing rapid deployment. This is the system used for WHO’s rVSV Ebola vaccine deployment in Ituri and North Kivu, Democratic Republic of the Congo, with over 135,000 vaccinated to date.

Picture 1.png