What is the problem/background?

The coronavirus disease (COVID-19) pandemic has so far affected almost 3 million people globally, with close to 200,000 deaths. The disease has been reported in over 200 countries, including Kenya where 363 cases had been reported as of 27^th April 2020. No vaccines or treatments are currently available for COVID-19. However, there are many COVID-19 vaccine candidates in development, but none of these are in development in Africa and no vaccine trials are currently ongoing in Africa. Vaccine performance from studies in other populations may not be generalizable to Kenya and other African countries. For instance, differences have been observed in malaria vaccine and ebola vaccine immune responses and reactions in European vs African populations. As the number of cases continue to rise globally, an effective vaccine remains the best way to control the pandemic and to safely relax social distancing and other restrictions. A candidate COVID-19 vaccine called ChAdOx1 nCoV-19 has been developed by our longstanding collaborators at the University of Oxford. The vaccine has been made using a platform, termed ‘ChAdOx1’, that is known to be safe in humans based on its use for making vaccines against other diseases. ChAdOx1 nCoV-19 has shown promise in a range of animal models of COVID-19 disease and is currently undergoing clinical trial in humans in the United Kingdom (UK) (ClinicalTrials.gov number: NCT04324606).

What questions are we trying to answer?

We plan to evaluate whether the ChAdOx1 nCoV-19 vaccine is safe and elicits good immune responses in adults in Kenya. The persistence of these immune responses will be investigated up to 12 months following immunization with a single dose of vaccine.

Where is the study taking place, how many people does it involve and how are they selected?

This study will be conducted among adults aged ≥18 years and will take place in the coastal counties of Kilifi and Mombasa, where high numbers of COVID-19 cases have been detected. The study will only enrol healthcare workers (HCWs) including doctors, nurses, clinical officers, pharmacists, mortuary attendants and allied healthcare professionals. HCWs have been prioritised due to their high risk of occupational exposure to COVID-19, hence their urgent need for protection.

What does the study involve for those who are in it?

Before enrolment, participants will undergo screening procedures to ensure they are in good health after they give written informed consent. This will include blood sampling for a series of tests to ensure eligibility, and collection of nose and throat swabs to screen for COVID-19. Individuals who are healthy and free of COVID-19 will then be randomised for vaccination with either a single dose of ChAdOx1 nCoV-19 (n=200) or a single dose of a licensed rabies vaccine (n=200) used as a ‘control’ for comparison. Participants will be followed up for 12 months, during which data on any vaccine-associated side effects will be collected and reviewed by an independent Data Safety and Monitoring Board (DSMB). The safety profile of the vaccine is expected to be good, and we will already have safety data from 800 adults participating in the UK vaccine trial before starting in Kenya. Safety assessments will be performed throughout the study. Blood, nose and throat swabs will be collected during scheduled follow up visits (days 14, 28, 84, 182 and 365) for monitoring of immune responses and acquisition of COVID-19. Participants will be directed to continue to adhere to the current COVID-19 preventive measures (including physical distancing, regular hand washing and cough/sneeze etiquette, as well as the infection control procedures in their workplace) even after vaccination since there is no evidence yet on the effectiveness of the vaccine. In the event that any of the study participants present with symptoms consistent with COVID-19 during the study, we will immediately notify public health authorities to facilitate their sampling, clinical management and quarantine as per the prevailing national guidelines. Participants will remain in follow up and their clinical outcome documented until the day 365 clinic visit when the scheduled final clinical assessment and sampling will be done.

What are the benefits and risks/costs of the study for those involved? 

If we demonstrate that the vaccine is safe and elicits good immune responses, participants may benefit in light of the current pandemic. Participants will also benefit by knowledge of their general health status, including whether or not they have COVID-19. Participants will also have close oversight and treatment support from the study team although this will primarily be for risk monitoring. The potential risk to participants is considered to be low and these mainly relate to phlebotomy and vaccination. During vaccination and when collecting blood samples, the participants may experience some discomfort on the injection site, which gets better after a short while. In general, vaccines against other diseases (e.g. malaria, tuberculosis, influenza, ebola) made using technology similar to that used for ChAdOx1 nCoV-19 have been given to several thousand volunteers (including children and the elderly) with a good safety profile.

How will the study benefit society? 

COVID-19 is currently a global pandemic with the number of cases and deaths continuing to rise on a daily basis. If found to be safe and good in generating protective immune responses, the ChAdOx1 nCoV-19 will be further developed for use in controlling COVID-19.

When does the study start and finish?

The study will start on receipt of ethical and regulatory approvals. Participants will be followed up for 1 year following vaccination, and we anticipate the total study duration including community engagement activities and post-study reporting to take approximately 2 years. Safety data from 800 adults participating in the ongoing phase I/II study in the UK (ClinicalTrials.gov number: NCT04324606) will be available before this study starts in Kenya. These UK safety data will be considered in the context of the Kenya trial protocol and shared with SERU and PPB for consideration as part of the approval decision process before vaccinations start in Kenya.