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Which COVID-19 vaccine works best?

Dr Karen Martin
Reviewed by Dr Karen MartinReviewed on 19.10.2023 | 5 minutes read
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While this deadly virus continues to disrupt the world, four vaccines have been approved in the US 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 modeling, 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 frequently being administered: Novavax, Pfizer-BioNTech and Moderna – all require two doses for maximum immunity. The Janssen vaccine by Johnson & Johnson just requires one dose, but is only recommended in certain circumstances due to the higher risk of adverse reactions. The Janssen and Novavax vaccines contain pieces of real virus, while the Pfizer and Moderna vaccines use pieces of virus grown in a laboratory 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 from dying, stops you from being hospitalized, stops you from 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 speak. If we look at a 90% effectiveness rate, it means that whatever your risk of getting COVID-19 before, now that 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 Organization (WHO) and the US Food and Drug Administration (FDA) both said – before vaccines were finalized – they would grant approval for the 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 that we have real-world data? They’ve proven to be extremely effective – against the initial strain, the Delta (or Indian) variant, and now the Omicron strain.

Analysis from the Centers for Disease Control and Prevention (CDC) has shown that vaccines are highly effective against preventing hospitalization. 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, and effectiveness second. Gathering data on safety starts in the lab, with tests and research on cells and animals. If everything looks good 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 vaccination and up to at least a year afterward. The regulator has been keeping a close watch and there were no significant safety concerns during this time.

Allergic reactions are very rare for any of the approved vaccines. However, for anyone who’s had any severe allergic reaction in the past they should talk to their doctor about which vaccine to receive.

There was much media coverage of brain clots (cerebral venous sinus thrombosis) or clots elsewhere in relation to the J&J/Janssen vaccine. These are a very rare occurrence, given the millions of doses administered, and scientists have now determined that there may be a pre-existing genetic risk. As a precaution, it is only offered in certain circumstances.

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.

Second doses are offered after 8 weeks in the US (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 may be able to 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 maybe, but all the vaccines are considered safe and effective. It may depend on which brand your vaccine center has been supplied with on any given day.

It may also depend on your age group, your medical history, and whether you are pregnant.

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 place, right? And any would work as well as another? Perhaps we need to think of it like that and focus less on pitting vaccine brands against each other.

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This article has been written by UK-based doctors and pharmacists, so some advice may not apply to US users and some suggested treatments may not be available. For more information, please see our T&Cs.
Dr Karen Martin
Reviewed by Dr Karen Martin
Reviewed on 19.10.2023
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