The things we know we don’t know about Covid-19 vaccines

South African and Brazilian variants have a mutation called E484K – an “escape mutation”

Any hope of the coronavirus pandemic coming to a slow but smooth end as more and more people are vaccinated against Sars-CoV-2 have been dashed in recent weeks. The emergence of coronavirus variants means the vaccination road is peppered with known unknowns.

As former US secretary of state for defence Donald Rumsfeld said in 2002: "There are known unknowns. That is to say, there are things that we now know we don't know."

In fact, much scientific research is based on investigating known unknowns.

So where are we on the known unknown road of coronavirus vaccination? Well, first it has to be said that one of the original unknowns – the length of time it would take to develop a vaccine against a brand new disease – has been answered a lot more quickly and effectively than anyone dared possible back in March 2020.


Mutations of a coronavirus microbe were always on the cards as a known unknown. Respiratory viruses, such as influenza, never sit still. It’s why we need a yearly influenza vaccine, made up of three different flu variants, which despite expert scientific opinion is still just a best guesstimate of what will work.

Although the overall effectiveness of the coronavirus vaccines already approved for use may be weakened a little, there is still strong evidence existing vaccines work well against the mutations that have emerged. But that hasn’t stopped scientists already looking to update the vaccine to make it more effective against the mutations that are being seen. And the good news is that is unlikely to involve the kind of large and lengthy medical trials needed to produce the original coronavirus vaccines.

Prof Andy Pollard, from Oxford University, told the BBC that tweaking a vaccine was a relatively quick process and would only need small trials before roll-out.

“I think the actual work on designing a new vaccine is very, very quick because it’s essentially just switching out the genetic sequence for the spike protein. Then there’s manufacturing to do and then a small-scale study. So all of that can be completed in a very short period of time, and the autumn is really the timing for having new vaccines available for use,” he said. An updated vaccine is likely to be given to people in the form of a one-dose booster.

Binding tightly to our cells

The UK was the first to identify a "variant of concern". It was found to be up to 70 per cent more transmissible than the original virus. Other concerning variants then emerged in South Africa and Brazil. They caused more consternation because they had a mutation called E484K – a so-called "escape mutation".

An escape mutation is one that is able to evade neutralising antibodies, making vaccines less effective.

According to Claire Crossan, a virologist at Glasgow Caledonian University, scientists are particularly interested in mutations occurring in the virus's spike protein, specifically the receptor-binding domain (RBD) of the spike protein. This section of the virus latches on to our cells and initiates infection. Mutations in the RBD can help the virus bind more tightly to our cells, making it more infectious.

“The immunity we develop to the coronavirus, following vaccination or infection, is largely due to the development of antibodies that bind to the RBD. Mutations in this region can allow the virus to evade or partially evade these antibodies. This is the reason they are called 'escape mutations'. E484K is one such mutation,” she says.

Scientists can’t chase every single mutation that emerges. But it is important to examine the combined effect of certain multiple mutations, especially those with “escape” potential, as opposed to studying only individual ones.

These are some of the current known unknowns around coronavirus vaccination. It’s a picture that constantly changes.

For now, the most important thing you can do is to roll up and be vaccinated as soon as your invitation arrives.