First results from Oxford COVID-19 vaccine trials

Over the last couple of weeks, the world news has been preoccupied with COVID-19 vaccines. At OUCRU, we have been excited by the results of trials testing the COVID-19 vaccine developed by our colleagues at the University of Oxford, in collaboration with British pharmaceutical company AstraZeneca.

The bottom line is that the trial news from all three new vaccines is very promising! All three vaccines – the ones from Pfizer and Moderna in the US, and the one from Oxford and AstraZeneca in the UK – appear to prevent people from developing the symptoms and disease of COVID-19.

Although there are differences in how the technology of ech of the three vaccines works, the idea behind what makes them effective is the same. All of the vaccines work by provoking a natural immune response in the body. The virus that causes COVID-19 has a particular shape. It is round, and has a lot of little spikes that pop out from the surface. These spikes are referred to as ‘spike proteins’, and they act a bit like a key, which the virus uses to infect cells. All three new vaccines cause the body to produce antibodies that block these spike proteins. So if someone who has been vaccinated comes into contact with the virus, their antibodies stop the virus infecting their cells and they do not develop disease (COVID-19).

The Pfizer and Moderna vaccines use a new kind of technology. The scientists who developed them took the part of the genetic makeup of the virus. They refer to this part as ‘messenger RNA’ – it’s a little bit of genetic code that the virus uses to make spike proteins. When virus messenger RNA is injected into a person, spike proteins get produced but not whole virus. Therefore, when the vaccine is injected into a person, their immune system notices the spike proteins and creates antibodies to them. Then, if a person is later exposed to the whole virus that causes COVID-19, the antibodies recognize the spike proteins on the virus and stop the virus from infecting cells and making the person sick.

The Oxford vaccine uses an older technology. Instead of using messenger RNA to make the spike proteins, the Oxford team used another virus, which is harmless to humans. They changed the virus so that it produced spike proteins after it is injected into the body, which causes the same protective immune response as the other two vaccines. Antibodies to spike protein are produced, and the person who has been vaccinated becomes immune to developing COVID-19 .

There are two main differences between the vaccines that use messenger RNA, and the Oxford vaccine. Firstly, RNA is not that stable at higher temperatures. So the Pfizer vaccine needs to be stored at -80 degrees Celsius. To put that in context – the average winter temperature at the South Pole is about -49C. So -80C is extremely cold. The Moderna vaccine is a little better – it can be stored between -10C and -20C, but this is still very cold. The biggest problem with these extreme temperatures is in transportation, especially in remote and under-resourced areas. While it is relatively easy to store and distribute these vaccines in big cities in wealthy countries, it’s much harder in other areas of the world. The Oxford vaccine still needs to be chilled, but it can be kept stable 2-4 degrees – fridge temperatures. This can still be tricky in hot countries, but is much easier.

The second big area of difference is in the price. Oxford and AstraZeneca produced their vaccine under the agreement that for as long as the pandemic is in effect, it will be made available on a not-for-profit basis. This means that neither Oxford nor AstraZeneca are making any profit from the vaccine, and therefore the cost per dose can be kept as low as possible. The prices of all the vaccines will be determined by many factors – but at the moment the Oxford vaccine is looking to be priced at around $4USD per dose, whereas the others will be significantly more expensive. The relatively low price of the Oxford vaccine is again good news for those in lower-income countries, and will help to ensure equality of access.

The big question on everyone’s mind is: but do they really work? All of the companies have announced efficacy rates following their clinical trials. Pfizer were first, claiming 90% efficacy. Moderna has an even high efficacy rate – 95%. And Oxford came out with several percentages: 70% overall. 62% if you get one dosing regime, and then the surprise – 90% with different dosing regime.

62% might only just be a passing grade at school, but in the world of vaccines it’s a solid A minus. 90% or higher efficacy rates in clinical trials are exceptional, with all 3 vaccines potentially achieving it. Many vaccines that are commonly in use have much lower efficacy rates. One of the world’s most commonly used vaccine – the TB vaccine – has an efficacy rate of less than 50%. Influenza is difficult to vaccinate against, because the virus changes each year, and so people need to get the right vaccine at the right time – but even then, the efficacy rate is often no more than 50 or 60 percent. Government regulators were well aware of this when they declared earlier in the year that they would approve any vaccine that had been shown to be safe, and had an efficacy rate of more than 50%. The high rates from these trials means that regulators can quickly move to approve, and this week the Pfizer vaccine has already been approved for use in the UK.
Oxford’s three different efficacy rates is one of those quirky stories in science, which points to the value of trying different things, and also to the value of looking for, accepting and examining mistakes. Because it was a mistake – to start with. In looking over early trial results, the investigators were surprised to see that one batch of around 3,000 participants had reported fewer side effects than expected. This kind of continuous review, and check, of trial results as the trial is still in progress is an important part of ensuring safety, and ensuring the trial protocols are being followed correctly.

In this case, they found that the trial protocols had not in fact been followed correctly. The vaccine is designed to be administered in 2 doses – first one, and then another a week later. But this group of participants received only a half dose the first time by mistake. This mistake doesn’t jeopardise or invalidate the trial results in any way. It’s still a valid result. But it does raise some more questions and point to the need to do more testing. The most obvious one being: what is the best dose? And what will the final efficacy of the Oxford vaccine really be? The team are not daunted by this. More testing was always on the cards anyway. For all of the vaccines, these results are only the first results, and all have more trials scheduled, in more contexts, looking to answer more nuanced questions.

And finally – what about those side effects? While the side effects that were reported weren’t pleasant – they were also no worse than expected. Participants reported the kind of symptoms that appear when the immune system jumps into gear – things like headaches, fever, joint aches, tiredness. These show up in any kind of vaccine that relies on the body generating an immune response, and the COVID-19 vaccines have been no different. But no more than 5% of people have developed these symptoms, and they get better on their own. No trial reported serious side effects, and with between 20,000 – 40,000 people in each trial, that’s very good news.