COVID vaccines update

To quote England’s Deputy Chief Medical Officer Jonathan van Tam, "a second penalty has hit the back of the net"; he was referring to the promising results for another Covid-19 vaccine, this one made by the US start-up Moderna. It followed hot on the heels of last week's announcement of similarly encouraging results from rivals Pfizer, who, having since reached the prescribed end-point for their phase 3 clinical trial, are applying to regulators in the US for emergency rapid approval of their vaccine there so it can be rolled out to patients. But to license the agent here in the UK, they also need to get the nod from our regulator, the MHRA. Normally, they would need to go through a trial process in this country too, but there is a special temporary rapid authorisation route known as regulation 174 for use in public health emergencies. MHRA Chief Executive June Raine said this week, "We look forward to receiving the full results of the trials as soon as possible, after which we will rigorously assess the evidence of safety and effectiveness of the vaccine." But what other vaccines are nearing the finishing line, and what does the healthcare profession make of the more than 90% protection rate reported by the two front runners? Chris Smith spoke with Peter Openshaw, an immunologist at Imperial College London...

Peter - It's highly statistically significant. And that's what we're looking for - is statistical significance. It's also much, much better than we expected. We were thinking it might be 50%, 60, 70% if we're really lucky; but nobody was really expecting over 90%.

Chris - The other crucial detail that's now being volunteered by Pfizer, perhaps because Moderna emphasise this point when they gave their results: they have covered a very broad brush stroke of the population when they've done these trials to make sure that their vaccine's relevant to everybody.

Peter - Yes, that's absolutely right. The latest press release is reporting efficacy in adults over 65, and they're also saying that older adults tend to report fewer side effects and milder adverse events.

Chris - Do the side effects look along the lines of what you would expect for a vaccine of any type, and are they within tolerable limits? Because one's always aware of the fact that with this coronavirus, maybe two thirds of people will have no symptoms if they actually catch the virus. And therefore, if you give them a vaccine that gives them any symptoms, you've actually given them a worse outcome than if they just caught it.

Peter - The sort of side effects that are being reported are normal, relatively mild side effects: maybe soreness of the arm, and then maybe a few people feel a little flu-ish for a day or two. I think if we compare that with this situation with catching COVID-19, a high proportion of people are getting really serious disease. So 1% mortality is 10 times worse than getting flu; and we're probably getting at least that number who are getting Long COVID syndrome. That seems also to happen in relatively young people with mild disease. So I've got no doubt at all that the vaccine is much better than catching the disease.

Chris - The one thing we haven't seen data for yet - and this is because no pharmaceutical company has a crystal ball - is what the longer term performance of these vaccines is going to be. They've only asked whether or not people caught it a short while downstream of having been given the vaccine, and that's a bit unhelpful, isn't it? Because we don't really know what will happen in nine months time.

Peter - Or a year, or five years. Yes, absolutely. But then that's unknowable. We inevitably don't know much about how long the antibody response is going to last. The sort of antibody levels that are induced by things like the Moderna vaccine, and also I think by the Pfizer vaccine; it exceeds that that you would expect from natural infection by maybe even a thousand fold. These are really strong antibody responses. So we're waiting to see obviously just how long it will persist and whether the protection is going to last more than one winter season.

Chris - The two vaccines we've heard about so far from Pfizer, BioNTech, and also Moderna - they're genetic vaccines. They've taken the piece of genetic code corresponding to the outer coat of the virus. What other vaccines are currently in trials or being developed? What other sort of irons have we got in the fire here?

Peter - Well, there's some pretty conventional vaccines from companies like Novavax. They've made some of the protein from the virus in insect cells, and then they've packaged it up into what's called nanoparticles. And that looks pretty good too; it's a much more standard approach to making a vaccine, and Sanofi and GSK also have some more regular type of vaccines. The Chinese in particular have been producing a vaccine which is based on inactivated, killed, whole virus. But then we've also got the vaccines which are genetically modified viruses - adenoviruses - which have been taken either from humans or from chimpanzees, and then they slot a gene into that, so that when that virus is injected it then throws out large quantities of the coronavirus spike protein, and the presence of the adenovirus makes the immune system really pep up and produce a lot of immune responses. That's another promising approach, but we don't know how it's going to compare.

Chris - Do you know what the timeline is for these other vaccines?

Peter - Well, the Oxford/AstraZeneca vaccine: we're expecting results anytime soon. I think certainly within the next few weeks everyone's anticipating that the first results may come through. Some of the other vaccines are going to take quite a bit longer, but I wouldn't be surprised if there's two or three that are reported this side of Christmas. The big question then is going to be how long it'll take to gear up and put vaccines into vials and syringes and get them out into arms, and that is no mean feat; that can sometimes take a lot longer than the initial development.

Chris - Do you agree with Sir John Bell, the UK government's vaccine lead, that we're going to be all back to normal by spring? Or do you think he was being a bit optimistic?

Peter - He and I actually are both optimists, but I think in practical terms there will be some groups of people within the population who are going to be vaccinated with the initial first round of vaccines, some of which may actually start to be injected this side of Christmas. But I think in terms of scaling up and being able to reach most of the population, that won't be until spring/early summer.