14 Nov 2020

Chris Smith: how exciting is Pfizer's vaccine news?

From Saturday Morning, 8:11 am on 14 November 2020

News that a collaboration between Pfizer and BioNTech has produced an effective coronavirus vaccine sent world stock markets soaring last week.

Pfizer said early results suggest the vaccine is more than 90 percent effective in preventing the disease among trial volunteers who had not previously been infected.

With no safety concerns as yet, the results have been described as "stunning".

Pfizer and BioNTech Announce Successful First Interim Analysis of their COVID-19 Vaccine Candidate in Current Phase 3 Trial

Photo: AFP

So, is this the breakthrough we have all been waiting for? And can people now start thinking about booking that overseas trip in mid-2021?

Dr Chris Smith, consultant clinical virologist at Cambridge University, and one of BBC Radio 5 Live's Naked Scientists sounds a note of warning.

“What we’ve got are lots of encouraging headlines, but no data to back it up, and it would be really rather nice to have some underpinning data, or for them to have waited until they had finished their Phase 3 trial, which is where their vaccine is at the moment, it’s not completed but they’ve got some directional preliminary findings which they’ve announced,” he told Kim Hill.

Although the 90 percent successful figure is making headlines, the 10 percent failure is a key factor, he says

“We want to know who are the 10 percent for whom this vaccine doesn’t work and why not?

“And if that 10 percent for whom it doesn’t work happen to be the same crowd of people for whom coronavirus is a death knell, then we’re not really any further forward through having a vaccine.”

Data we still need concerns who responded to it, what sort of age range they are in and whether any were participants with underlying chronic health conditions or immune disabling conditions – we also need to know long immunity lasts for, Dr Smith says.

“Those are the questions we do need to see answers to before we can pop too many champagne corks.”

The speed with which the vaccine has been developed is unprecedented, but then we are in unprecedented times, he says.

“There is no precedent for a pandemic that has caught the world with its trousers down in the way that this one has, but normally what happens is pharmaceutical companies will go through ten years of testing and research and development with a 90 percent failure rate to get their success story out there, and then they begin to market them.

“It’s not that usual for someone midway through a phase 3 trial to then announce results in this sort of way.  One wonders if someone was either going to leak something or if there is some other reason why.”

He is unclear why an announcement should have been made so soon in the vaccine’s development.

“Unless it’s to give us all, the world’s morale, a shot in the arm,” he says.

He also has criticism of the numbers in the Pfizer trail.

“If you look at the data, they’ve done this trial, they say, on 44,000 people, and that was placebo-controlled trial.

“Roughly half the people get the placebo, the other half get the real deal vaccine.

“You follow that up and what you are looking for is an excess of infections in the group that have had the placebo.”

To make a case for the vaccine it must protect the people who have had the vaccine much more than the people who haven’t, he says.

“But there’s only been about 90 infections that we know of, obviously the vast majority of those in the placebo group, but that’s not very many people who have actually caught it in the placebo group for us really to have a clear idea about things.”

We effectively have one chance to get this right, he says.

“Because there will be enormous backlash if this goes wrong. Whoever is first through the gate and starts putting vaccines into people, if it goes wrong, the impact will be so dramatic because it will induce a state of paralysis across all vaccines because it will massively fuel both the anti-vax but also the vaccine hesitancy stakes.”

Even if the next one that comes along is perfect, people will be sceptical of its efficacy and safety, he says.

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Photo: Facebook

The type of vaccine Pfizer has developed is a messenger RNA vaccine, a “completely new way of doing things,” he says.

“What they’ve done is take the genetic code of the virus, specifically the part of the genetic code that it uses to make its surface coat protein, the ‘S’ or spike protein. This is the bit of the virus that is the business end, that grabs hold of our cells and it engages with them and forces the virus into our cells.

“If you make antibodies against that structure it stops the virus invading our cells, so it is a good target.”

A piece of genetic code is taken from the virus, the MRNA, and wrapped in an oily bubble.

“You make billions of these tiny, oily bubbles, the oil is there to stabilise this and to help it get into cells.

“You inject this preparation into a muscle and the surrounding cells pick up these packages, they unwrap them, get the genetic code out, read it and then use that genetic code to make the outer coat of the virus as though those cells had been infected with the virus for real - obviously, they haven’t, they’ve just got the genetic message corresponding to a bit of it - and this is then displayed to the immune system just as if they had been infected with a virus.”

This displays the virus in a context that shows it is really growing inside those cells, he says.

“This shows the immune system what the virus does to that cell, when it makes this protein and what it looks like and it drives a pretty potent response, both to make anti-bodies, which are molecules that can stick on to things that can neutralise them, and also white blood cells called cytotoxic T cells that can go around inspecting cells in the body and looking for signs that viruses are growing in them and destroying those cells.”

This gives you both arms of the immune response, he says.

“But it’s not been done for a coronavirus before, it’s not been done in a human before so it’s a first on many levels.”

A genetic vaccine such as this has sound advantages, Dr Smith says.

“The great attraction of a genetic vaccine like this is that you can make enormous amounts of it very quickly and relatively cheaply.”

It is also possible to tweak it when the virus mutates. Such as when it enters a new species, as it has done with mink in Denmark which has the potential to bypass human immunity conferred in a vaccine, he says.

“That could pull the rug from under vaccines that you can’t update, but with a genetic vaccine like this you could take the message corresponding to the altered version of the virus, and you could add that into the mix and update your vaccine to use exactly the same mechanism, you’ve got the safety track record you know works

“But you can make it agile and make it respond to a changing infectious threat like this one.”

Pfizer says the vaccine it is developing needs two doses.

“The way the immune system works is it is an adaptive immune response, you start with a blank sheet, you make an immune repose to things that you see and every time you re-encounter that thing you make the immune response even better.

“By giving people two hits of the vaccine, you drive a response, once you establish what’s called immune memory, which is a whole suite of cells sitting in the body that have memory of having encountered that particular threat and know how to make anti-bodies against and how to make white blood cells that can kill virus-infected cells.

“If you come back with another stimulus to remind the immune system what it leaned before it’s almost like sending you back for your repeat driving test.”

The need to keep this particular vaccine at very low temperatures are to do with its chemistry, in much the same way chops will last longer in the freezer than the fridge, he says.

“Something like this is very precious, you don’t want half of it going off.”

Administering such a vaccine population wide will be a logistical challenge, he says. But its strategic deployment could make this more realistic in a short time frame.

“One group at the University of Oxford have done a bit of modelling and what they have proven is that if you hit about 5 percent of people the most vulnerable you can reduce your death rate by 70 percent straight away

“So, by being strategic, especially when these things are in limited supply, we know 80 percent of people will be absolutely fine if they catch coronavirus, 20 percent will not be fine, but it’s only about 20 percent of that 20 percent who will have really serious problems.

“If we target those people most at risk, and the people caring for those people, we can block the majority of the transmission into groups of people who really have a lot to lose if they catch this and that makes the problem much more tractable.”

He anticipates the first doses will be available early next year.

“I think it will be early next year for the most vulnerable cases, and assuming other vaccines come along, or other things begin to scale up, next UK summer for the rest of the population to begin to see the start of vaccinations at some kind of scale.”

It is also important to remember there are many other vaccines, using different mechanisms in development, he says.

“There are 30 now in phase 3 clinical trials and that’s really good, because we know if you go and ask someone running a pharma company they will tell you that their business model is entirely based around a 90 percent failure rate.

“They succeed 10 percent of the time because they are very good at it because this is really hard to do.”

There are more than ten different type of vaccines being developed, he says.

“This is fantastic because it is not a given it will be a one-horse race, it’s almost certain there will be certain vaccines that work really well in certain contexts on certain people in certain circumstances, and they will be rubbish for other applications.”

For example, a low temperature vaccine is useless in a poor country with unreliable power supply.

“So, you need a vaccine that is stable at high temperatures.”