Combined phase II/III trials for a potential vaccine being developed at the University of Oxford’s Jenner Institute to protect against COVID-19 may be continuing in the UK, but they remain paused in the United States.
Global trials of the vaccine were halted after a British participant developed symptoms of transverse myelitis, a neurological disorder which causes the spinal cord to become inflamed and damages the myelin layer which protects nerve cell fibres. Although trials in the United Kingdom, South Africa and Brazil were resumed throughout September, the Food and Drug Administration (FDA) regulatory body has halted trials in the United States until they are satisfied the participant’s adverse reaction was not caused by the vaccine.
Dr Anthony Fauci, the prominent immunologist advising the White House Coronavirus Taskforce, described the interruption as “unfortunate” but emphasised that it is not unusual for vaccine trials to be halted. “It’s really one of the safety valves that you have on clinical trials such as this”, he told CBS on 9 September.
Although investigating potential side-effects is an established part of the vaccine development process, there are concerns that if the FDA does not allow the trial to continue, it could reduce the data available to scientists to judge the efficacy and safety of the vaccine. Most new drugs and vaccines go through three phases of testing before they are made available to patients. Some national regulatory bodies, including the FDA, may demand additional rounds of testing. Phase III trials involve thousands of patients to provide a large sample size for scientists to determine how effective the vaccine is, but also if there are any side effects or groups of people who cannot receive the vaccine safely.
The Oxford vaccine requires two injections to be given at 28 day intervals. While 18,000 participants across the UK, Brazil and South Africa are on track to receive their second dose, 30,000 American participants may miss theirs or at least have it delayed unless the FDA allows the trial to continue soon. It is not clear what the implications of this delay would be. Eleanor Riley, Professor of Immunology at the University of Edinburgh told The Times that delivering the second dose a longer interval after the first than 28 days may leader to better outcomes. “However, changing the interval halfway through a trial can be problematic”, she added. If the American cohort of participants are not vaccinated according to the determined schedule, they may have to be excluded from the overall analysis of data.
The SARS-Cov-2 virus, which causes Covid-19, is covered with club-shaped spike proteins which it uses to infect human cells and hijack them to produce more viruses. Spike proteins are also recognised by the body’s immune system, causing it to produce antibodies to combat the infection.
The Oxford vaccine uses a harmless adenovirus to introduce a sequence of DNA into a human cell, causing it to make the spike proteins which cause an immune reaction. It is hoped that this method will allow the body to develop immunity to SARS-Cov-2, without causing a vaccinated individual to become unwell or contagious. Ideally that this will allow people with pre-existing conditions to receive the vaccine and reduce the risk of patients developing side-effects.
If the vaccine passes its phase III trials and is found to be both safe and effective, it could allow countries around the world to lift restrictions put in place to limit the spread of Covid-19.
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