How well do first and second vaccine doses work against Covid-19?

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Is it risky or wise to delay the second dose of Covid-19 vaccine? Critics warned against the UK government policy of leaving a longer gap between doses of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines. Now we have more data, so what do we actually know?

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A healthcare worker holds up a dose of a Covid-19 vaccine.
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A staff nurse at the Royal Cornwall Hospitals NHS Trust prepares to administer Covid-19 vaccinations. 

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How long after vaccination does immunity take to develop?
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How long after vaccination does immunity take to develop?
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Immunity takes a while to build up. If you had your first Covid-19 vaccine dose yesterday, then you are not protected yet. Your body needs to spend time responding to the vaccination before it can produce an effective immune response.

It seems that some protection starts to appear about 2 weeks after the first dose, and then this increases over time. But after a longer time – we don’t yet know how long – this protection is likely to start to fade again. So you will need a second booster dose to make sure your immune system can consolidate this protection for the long term.

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How long after the first dose should you have the second dose?
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How long after the first dose should you have the second dose?
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The UK introduced its policy of leaving a 12-week gap between Covid-19 vaccine doses at the end of December. This is at the top end of the range recommended by the makers of the Oxford-AstraZeneca vaccine (4 to 12 weeks) but is much longer than recommended for the Pfizer-BioNTech vaccine (3 weeks). 

Leaving the second dose too late is risky, because the effects of the first dose might start to weaken. But giving the second dose too soon is also risky, because your immune system needs time to fully react to the first dose so that it can then get maximum benefit from the second. In general, a 12-week gap between vaccine doses would not be long enough for that initial protection to fade.

For the new Covid-19 vaccines, we don’t yet know what the ideal gap is – it takes time to test this. But the evidence is increasingly positive about longer delay.

For the Oxford-AstraZeneca vaccine, data from clinical trials suggests that a single dose gives good protection against illness for more than 12 weeks, and that the booster effect of the second dose is stronger when the gap between doses is longer. 

For the Pfizer-BioNTech vaccine, we have less specific evidence on this question. But a review of unpublished data for Canada’s National Advisory Committee on Immunization looked at the Pfizer-BioNTech and the Moderna vaccines together – both were created using a similar mRNA technology. It found that leaving 6 weeks between doses resulted in no less protection than a 3-week gap.

And real-world observation is already showing that first doses maintain their strong benefits for longer than the initial 3 weeks. Public Health England and Public Health Scotland are monitoring illness rates among adults who have and haven’t been vaccinated, and findings so far show that both the Pfizer-BioNTech and the Oxford-AstraZeneca vaccines give strong protection from serious illness and reduce hospitalisations more than 4 weeks after the first dose.

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Can you still get ill with Covid-19 after vaccination?
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Can you still get ill with Covid-19 after vaccination?
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The new vaccines are very good, especially considering that they were developed in record time. But they’re not perfect. The highest estimates of their peak efficacy are above 90%, but not quite 100%. After you’re vaccinated, it is possible that you could catch Covid-19. But if you do get ill, it’s much less likely to be severe and you’re much more likely to recover without needing to be hospitalised.

Remember, immunity takes weeks to properly develop after getting your first dose, so during that time you may still be at some risk.

There’s also the danger of new coronavirus variants emerging that might be able to avoid the vaccines’ effects. Scientists are already looking at ways to adjust the vaccines to cope with such variants, so in the future we might need occasional booster jabs to keep us protected.

We might even need boosters at some point regardless of any variants, as it’s possible that the protection might fade in the long term.

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Do the vaccines prevent you from spreading coronavirus?
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Do the vaccines prevent you from spreading coronavirus?
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We know that vaccination can stop you from getting seriously ill if you catch the virus, but an early worry was that it might not stop you from carrying the virus and spreading it to others. Now, evidence is starting to come in showing that vaccination can also reduce the spread of infection.

The findings so far are good for the Pfizer-BioNTech vaccine. Studies of healthcare workers in Israel and in England have found not just a big drop in illness but a drop in infection too. We don’t yet have direct evidence on whether the same is true for the Oxford-AstraZeneca vaccine, but research is underway looking into this. 

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Why did the UK decide to extend the gap between doses?
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Why did the UK decide to extend the gap between doses?
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UK cases of Covid-19 were surging in December, along with hospitalisations and deaths, and there was a risk that the NHS could be overwhelmed. In light of this, health authorities decided that it would be better to give the protection of a first dose to as many people as possible, as fast as possible. That meant delaying second doses, on the grounds that they would add only limited extra protection to people who already had significant immunity from their first dose.

This policy was recommended by the independent experts on the Joint Committee on Vaccination and Immunisation – an independent expert group that advises the UK health departments – and the UK’s Chief Medical Officers agreed

Ideally, researchers would run a set of clinical trials to compare different dosing schedules and then authorities would make policy based on plenty of solid data. But in the face of a public health emergency, waiting would have cost lives. The decision was based on limited data from the vaccine trials in 2020, coupled with expert judgement about how vaccines generally work.

Evidence that has appeared since then is, so far, vindicating that decision.

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Which other countries are delaying second doses?
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Which other countries are delaying second doses?
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In early March, Germany changed its policy to leave a 6-week gap between doses of Pfizer-BioNTech and 12 weeks between doses of Oxford-AstraZeneca.

Canada has gone even further, changing official guidance to support a 4-month gap.

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What about 'mixing and matching'?
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What about "mixing and matching"?
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There is no evidence yet on whether switching vaccines between doses can make any difference, but some immunisation programmes for other diseases do this because the results are better. There are already trials underway to test whether this might work for the Covid-19 vaccines.

In the meantime, the UK government says that people should get a second dose of the same vaccine as their first dose, as do other governments around the world. However, if supplies of that vaccine are unavailable, or information has been lost on which the first dose was, the UK guidance is that it may better to give a dose of whichever is available rather than no second dose at all.

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What happens next?
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As the vaccine roll-out continues, we need to keep reducing the spread of the virus by following guidelines on wearing masks, washing hands and avoiding face-to-face contact wherever possible. This applies even after receiving the first dose, because immunity takes time to build up.

Scientists will need to keep monitoring the appearance of new variants across the world, and devise ways to modify the vaccines if needed.

Finally, it is crucial to make sure vaccination is rolled out speedily and equitably across the globe, not just in the UK and other rich countries. The more people worldwide who remain exposed to the virus, the more opportunity it will have to mutate into a more harmful form. In a pandemic like this, the interests of any one country merge together into the interests of the whole human race. 

This article was first published on 18 January 2021, and updated on 22 March 2021.

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Critics warned against the UK policy of leaving a longer gap between doses of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines. Now we have more data, what do we actually know?

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A healthcare worker holds up a dose of a Covid-19 vaccine.
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Hugh Hastings / Stringer / Getty
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A staff nurse at the Royal Cornwall Hospitals NHS Trust prepares to administer Covid-19 vaccinations. 

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A healthcare worker holds up a dose of a Covid-19 vaccine.
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Is it risky or wise to delay the second dose of Covid-19 vaccine? Critics warned against the UK government policy of leaving a longer gap between doses of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines. Now we have more data, so what do we actually know?
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