A publication in The Lancet by the University of Oxford reveals their Phase I/II COVID-19 vaccine clinical trial is producing a strong immune response.
This randomised controlled trial saw 1,077 healthy volunteers, aged 18-55, receive either the active ChAdOx1 nCoV-19 vaccine or a placebo MenACWY vaccine. ChAdOx1 is an adenovirus vector vaccine that causes the common cold in chimpanzees but is genetically altered so it cannot infect human cells. This vector is used in other vaccines, such as Ebola, so approval for its use in COVID-19 trials was quick. It has also been shown to generate a strong immune response after a single dose in other vaccines, so is suitable for a COVID-19 vaccine where accessibility must be widespread and costs kept to a minimum. The vector expresses the SARS-CoV-2 spike protein for the immune system to mount a response against. This provides protection if the coronavirus is encountered as the immune system recognises the spike protein as foreign and attacks it, preventing infection. A MenACWY placebo was chosen over an inert placebo so that the usual vaccine side effects, like chills, muscle aches and pain at the injection site, would be experienced by all volunteers so they would not know which vaccine they had received. This prevents creating a bias in the results. Ten of the ChAdOx1 nCoV-19 vaccine-receiving volunteers were given a booster dose 28 days after the first dose.
‘I’m pleased to have the opportunity to play a very small part in a trial that the whole world is watching.’ – Richard Fisher, Oxford vaccine trial volunteer.
The results indicate no early safety concerns, other than normal vaccine reactions that were treated with paracetamol. The vaccine is shown to induce both innate and adaptive immune responses, which are key in preventing infection if the virus is contracted. The vaccine provokes a T cell response within 14 days; their role is to attack and kill infected cells and produce a memory response in case of a second exposure. An antibody response was seen within 28 days. Antibodies circulate in the bloodstream and neutralise the virus before it can infect cells. Those that received a booster dose were shown to produce a stronger immune response than volunteers with a single dose as their antibodies were more specific to the spike protein, having encountered it twice, so they could combat the virus quicker and more efficiently.
What happens next?
Now that the vaccine is shown to be safe, its administration can be expanded. Elderly people have proven to be most vulnerable to COVID-19 so trialling the vaccine in elderly volunteers would be useful, as well as trialling it in under-18s.
The University of Oxford, in collaboration with AstraZeneca, have received £84 million in Government funding to accelerate the vaccine’s development.
The next step is a Phase III clinical trial as part of a global clinical programme. A trial recruiting 30,000 US volunteers, a paediatric study and trials in low- to middle-income countries, including Brazil and South Africa, are commencing. Should these trials prove successful, AstraZeneca are committed to supplying more than 2 billion doses in the next year to fulfil their promise of broad and equitable access to the vaccine.