Safety and Immunogenicity of a candidate MERS-CoV vaccine (MERS001)
Research type
Research Study
Full title
A phase I study to determine the safety and immunogenicity of the candidate Middle East Respiratory Syndrome Coronavirus (MERS-CoV) vaccine ChAdOx1 MERS in UK healthy adult volunteers
IRAS ID
231515
Contact name
Adrian Hill
Contact email
Sponsor organisation
University of Oxford, CTRG
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Reserach Summary
The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has been identified as one of the most worrying newly emerging outbreak pathogens by many global agencies and expert groups. The disease was first described in 2012 and is now endemic in Saudi Arabia. It has since spread to different countries in the Middle East and other regions, including a recent outbreak in South Korea. More than 2000 cases of MERS-CoV with 720 deaths in 27 countries have been reported. \nThe disease is caused by a Coronavirus and is spread by droplet infection of the airways. Dromedary camels are now recognised as the source of zoonotic infections and occupational exposure can lead to seroconversion. Human to human transmission, especially in hospital environments, have been responsible for the majority of cases seen in recent outbreaks. The clinical spectrum of MERS-CoV infection varies from asymptomatic or mild respiratory symptoms to severe acute respiratory disease and death. Severe illness can cause respiratory failure that requires mechanical ventilation and support in an intensive care unit. MERS-CoV has a reported case fatality rate of approximately 35%. The virus appears to cause more severe disease in the elderly, immunosuppressed and those with chronic diseases such as cardiovascular disease and diabetes.\nThe disease has been chosen as a very high priority disease for accelerated vaccine development by the WHO. Vaccination of workers who are occupationally exposed to camels would prevent them from becoming infected and limit the transmission of the virus to the wider population, in particular those at an increased risk of death.\nIn this study, healthy adult volunteers will receive a single dose of a new candidate MERS-Cov vaccine at different doses. The objective of this first-in-human study is to find the optimal dose of the vaccine, balancing immune responses and profile of adverse events \n\n
Summary of Results
Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerged virus. It infects humans and animals and can cause severe illness and death, especially in individuals with underlying health conditions. There are no vaccines against the disease currently. Here we tested a newly developed vaccine called ChAdOx1 MERS which is a “viral vector” type of vaccine. The ChAdOx1 MERS vaccine consists of a genetically modified virus called an adenovirus, which is unrelated to MERS, that has had a single gene from the MERS virus inserted into its genetic code.
How was the trial performed?
The trial was the first time ChAdOx1 MERS had been tested in humans. It took place at a single location in the UK, the Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford. We enrolled healthy volunteers aged between 18 and 50 years. Initially the trial had three groups, corresponding to a single vaccination with either a low, medium or high dose of ChAdOx1 MERS. We first enrolled individuals to the low dose group, before enrolling to the medium dose group and then the higher dose group. The trial design was later amended to add in two further groups that would receive two medium doses of vaccine either 6 months (group 4) or 4 weeks (group 5) apart.
What were the objectives of the study?
The main objective of the study was to assess the safety of the vaccine by asking participants to report any symptoms or illnesses they experienced. The secondary objective was to measure the immune responses induced by the vaccine. This was done by examining blood samples to measure antibody levels and white blood cell activity against MERS. Participants were followed up for up to 12 months.
What were the results of the study?
A total of 29 participants were enrolled into the study. In the first part of the study 6 were enrolled in the low dose group, 9 in the medium dose group and 9 in the high dose group. In the second part of the study 3 were enrolled to group 4 (two medium-doses of ChAdOx1 MERS 6 months apart) and 2 to group 5 (two medium-doses 4 weeks apart). All participants in groups 1 to 3 and 5 received their assigned vaccines. Only 1 out of 3 participants in group 4 received both doses of vaccine as 2 participants withdrew from the trial after receiving a single dose.
The vaccine was well tolerated. Post-vaccination symptoms that were reported by volunteers were mostly mild in intensity, but some (approximately one quarter of reports) were described as moderate. The higher dose group reported more symptoms than other groups, with 5 out of 9 reporting short-lived fevers. No serious adverse events related to vaccination were seen during the study. Two participants reported serious adverse events during the follow period of the study but these were assessed as being unrelated to the study vaccine.
The trial results showed that the antibodies and T-cells that target the MERS virus rose after vaccination, indicating that the vaccine is eliciting an immune response.
The study was ended early due to the COVID-19 pandemic occurring at the time. Enrolment and follow up of groups 1 to 3 was completed before this point. However, recruitment to the two dose groups (groups 4 and 5) was not completed.
What do the results mean?
ChAdOx1 MERS was tolerated at all doses used in the study and no safety issues were found. The vaccine is able to induce detectable antibody and t-cell immune responses against MERS. This initial first-in-human study supports further development of the vaccine in larger clinical trials.REC name
South Central - Oxford A Research Ethics Committee
REC reference
17/SC/0552
Date of REC Opinion
21 Nov 2017
REC opinion
Favourable Opinion