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Which COVID-19 vaccine works best?

Dr Roger Henderson
Reviewed by Dr Roger HendersonReviewed on 13.10.2023 | 6 minutes read
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While this deadly virus lays siege to the world, four vaccines have been approved in the UK to combat it. But which is the safest and most protective; which is the best? Perhaps it’s best to debunk this from the start: there is no "best" vaccine. They’ve all been approved through a rigorous regulatory process after initial computer modelling, then laboratory tests and clinical trials, and now testing on millions in the real world. They have all performed to an exceptionally high standard.

There are three vaccines currently being administered: Oxford-AstraZeneca, Pfizer-BioNTech and Moderna – all require two doses for maximum immunity. The Janssen vaccine by Johnson & Johnson has been approved by regulators but won’t be available until later in the year – this just requires one dose. The Janssen vaccine is a similar technology to the AstraZeneca vaccine, and the Pfizer and Moderna vaccines are similar in both using mRNA technology.

But it’s likely you have questions about each, and it can be hard to sift through all of the information coming at us. We'll help you make sense of what we know so far.

Which one works best?

This concept is termed effectiveness, and means how well it produces a desired or intended result. What's the intended outcome of the COVID-19 vaccine? To reduce the chance of us catching and becoming ill with COVID-19. Where the COVID-19 vaccine is concerned, this can be measured by a number of outcomes – whether it stops you dying, stops you being hospitalised, stops you developing symptoms when infected, or whether you can dodge infection altogether.

This is usually reported as a percentage, but what does that mean? This is a tricky concept – do skip this paragraph if this is too much science chat. If we look at a 90% effectiveness rate, it means that whatever your risk of getting COVID-19 before, now you’ve been vaccinated, the risk is reduced by, for example, 90%. In trials, they could compare results from a group that received the vaccine and a group that received a dummy version (placebo). It does not mean that 90 out of every 100 people in the trial that were vaccinated escaped COVID-19 (and 10 caught it).

So what’s a good rate? The World Health Organisation and the US’s Food and Drugs Administration both said – before vaccines were finalised – they would grant approval for effectiveness of 50% and above. So you’ve halved your chance of getting COVID-19 (or whichever desired outcome is picked). Sounds pretty good, eh?

So how have the vaccines performed now we have real world data? They’ve proven to be extremely effective – against the initial strain, the Alpha (or Kent) variant that emerged just before Christmas in the UK, and now the Delta (or Indian) variant that accounts for most cases in the UK currently.

Analysis from Public Health England in June 2021 showed two doses of each vaccine were highly effective against the Delta variant: the AstraZeneca vaccine was 92% effective against preventing hospitalisation, the Pfizer vaccine was 96% effective. And despite a very high number of cases, the death rate from COVID-19 has been greatly reduced by all vaccines.

Analysis has shown that the vaccines are also significantly protective against severe disease in those most at risk – the elderly, immunosuppressed and those with significant health problems such as diabetes, kidney or liver disease and severe asthma.

The bottom line is that these vaccines are working far better than could be imagined, in trials and in the real world, and a few percentage points between them is trivial in the face of beating this virus.

Which one is safest?

Clinical trials value safety first, effectiveness second. Gathering data on safety starts in the lab, with tests and research on cells and animals. If everything looks at a certain level of safety, the vaccine teams can move on to human studies. Despite the record speed at which COVID-19 vaccines have been developed, no steps have been skipped in the usual high standards of clinical trials.

Trials for each vaccine included tens of thousands of volunteers in countries all over the world. The first groups were the young, fit and healthy. The usual procedure in trials is that if there were no safety concerns, trials expand to more vulnerable groups, such as those with medical conditions or the elderly.

Research teams recorded any symptoms or illness, from the mildest to the most severe, both at the time of vaccine and following up that will go on for at least a year afterwards. The regulator has been keeping a close watch and there were no significant safety concerns during this.

Allergic reactions are very rare for any of the approved vaccines. However, the regulator has said that anyone who’s had any severe allergic reaction in the past should have the AstraZeneca vaccine rather than the Pfizer, as a precaution.

There was much media coverage of brain clots (cerebral venous sinus thrombosis) or clots elsewhere in relation to the AstraZeneca vaccine and the Janssen vaccine. These are a very rare occurrence, given the tens of millions of doses administered, and scientists have now determined that there may be a pre-existing genetic risk. As a precaution, it is not offered to those under 40, in pregnancy, or those with particular low platelet conditions.

Despite much concern, it’s worth saying that these cases are very rare, and COVID-19 infection brings with it a much higher chance of life-threatening clots – in the lungs, brain, anywhere – than any vaccine.

Why are they given weeks or months apart?

With previous COVID-19 strains, evidence suggested that the first dose gave excellent immunity, and a second dose topped this up and made protection last longer. It takes about two weeks after a dose for immunity to build sufficiently.

The Delta variant now accounts for almost all cases in the UK, and is set to become the predominant strain worldwide, so data has recently focused on how well the vaccines combat this particular strain. With the Delta variant, the first vaccine dose is fairly low in effectiveness (30% to 36% protective against symptomatic infection), but two doses boost immunity to 67% for AstraZeneca and 88% for Pfizer. Prevention of hospitalisation or death is even higher for both vaccines. To make the most of the immune system’s response, these doses need to be given with time in between.

Second doses are offered after 8 weeks in the UK (and within 12 weeks), to enable the most protective immune response to combat COVID-19. The gap used to be different for each vaccine, based on how each manufacturer set up clinical trials, but gaps are now the same for all.

If there are exceptional circumstances – such as you are awaiting an organ transplant or chemotherapy and delaying your second dose could have serious consequences – you can receive a second dose after 3 weeks. Planning a trip abroad is not usually accepted as a valid reason to fast-track your second dose.

Will I get a say in which one I get?

The long and short of it is no, you don’t get a choice, and all the vaccines are considered safe and effective. It depends which brand your vaccine centre has been supplied with on any given day.

It will also depend on your age group. Those aged 40 and under or women who are pregnant will be offered Pfizer or Moderna. Those in the older age group, with a history of severe allergic reaction or anaphylaxis, or those with allergies to certain components of the mRNA vaccines, will be offered AstraZeneca.

Think about other vaccines – do you know who makes your flu vaccine? Did it occur to you to mind? You just trusted the balances and checks were in check, right? And any would work as well as another? Perhaps we need to think of it like that and focus less on pitching vaccine brands against each other.

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Dr Roger Henderson
Reviewed by Dr Roger Henderson
Reviewed on 13.10.2023
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