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Covid-19 vaccines: to delay or not to delay second doses
Opinion
How do you take your vaccine—one lump or two?
On 30 December the four UK chief medical officers announced that the second doses of the covid vaccines should be given
towards the end of 12 weeks rather than in the previously recommended 3-4 weeks. Gareth Iacobucci and Elisabeth Mahase
look at the questions this has raised
Why has the government taken the step to delay the second dose?
In a letter sent to healthcare staff on 30 December NHS England said the decision had been taken to prioritise giving theI first Accept
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doses of vaccine (whether the Pfizer and BioNTech one or that of Oxford University and AstraZeneca) to as many people as
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availability of the AZ [AstraZeneca] vaccine reduces, but does not remove, this major problem. Vaccine shortage is a reality that
cannot be wished away.”
In their joint statement the chief medical officers said that data provided to the Medicines and Healthcare Products Regulatory
Agency (MHRA) showed that, although optimal efficacy was achieved through two doses, both vaccines “offer considerable
protection after a single dose, at least in the short term.”
Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said, “In an ideal
world, decisions about treatments would only be made within the exact parameters of the trials which have been conducted. In the
real world, this is never so . . . We know that vaccinating only half of a vulnerable population will lead to a notable increase in
cases of covid-19, with all that this entails, including deaths. When resources of doses and people to vaccinate are limited, then
vaccinating more people with potentially less efficacy is demonstrably better than a fuller efficacy in only half.”
In the case of the Oxford-AstraZeneca vaccine, PHE said, “High protection against hospitalisation was seen from 21 days after
dose one until two weeks after the second dose, suggesting that a single dose will provide high short term protection against
severe disease . . . An exploratory analysis of participants who had received one standard dose of the vaccine suggested that
efficacy against symptomatic covid-19 was 73% (95% CI 48.79-85.76%).”
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Richard Vautrey, chair of the BMA’s General Practitioners Committee, said, “The decision to ask GPs, at such short notice, to
rebook patients for three months hence will also cause huge logistical problems for almost all vaccination sites and practices. For
example, to make contact with even just 2000 elderly or vulnerable patients will take a team of five staff at a practice about a
week, and that’s simply untenable.”
He said that bookings for the oldest and most vulnerable members should be honoured.
What are patients told about their behaviour after one dose?
Patients are given a leaflet when attending vaccine appointments,9 and this has been updated to reflect the latest changes to
dosing. It tells patients that it takes one to two weeks for protection to build after the first dose. It advises, “Like all medicines, no
vaccine is completely effective, so you should continue to take recommended precautions to avoid infection. Some people may
still get covid-19 despite having a vaccination, but this should be less severe.”
But Andrew Pollard, the head of the Oxford Vaccine Group and chief investigator into the trial of this vaccine, said that extending
the gap between vaccines made biological sense. “Generally, a longer gap between vaccine doses leads to a better immune
response, with the second dose causing a better boost. (With HPV vaccine for girls, for example, the gap is a year and gives
better responses than a one month gap.) From the Oxford vaccine trials, there is 70% protection after the first dose up to the
second dose, and the immune response was about three times greater after the second dose when the second dose was
delayed, comparing second dose after four weeks versus second dose after 2-3 months,” he told The BMJ, referring to the
MHRA’s summary of product characteristics.11
“With the Pfizer vaccine, there are no published data comparing shorter and longer gaps between doses because all participants
had the second dose at 3-4 weeks. However, the biology is straightforward and will be the same as with all vaccines . . . The
immune system remembers the first dose and will respond whether the later dose is at three weeks or three months.”
In a statement the British Society for Immunology said, “Most immunologists would agree that delaying a second ‘booster’ dose of
a protein antigen vaccine (such as the two approved covid-19 vaccines) by eight weeks would be unlikely to have a negative
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effect on the overall immune response post-boost. We also would not expect any specific safety issues to arise for the individual
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due to delaying the second dose, other than an increased potential risk of disease during the extended period due to lowered
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protection.”
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However in a interest
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that less was known about the behaviour of the Pfizer vaccine because of the novel mRNA technology it uses.12 “Maximising
coverage with the first dose as intended by the CMOs could come at increased risk to already high risk/priority groups,” they said.
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They called for the second dose of this vaccine to be provided at day 21 “until the MHRA and/or JCVI [Joint Committee on
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A spokesperson for the Department of Health and Social Care for England said, “As agreed by all four UK chief medical officers
and the medical experts at the independent Joint Committee on Vaccination and Immunisation, the data provided by the
manufacturers demonstrated that both vaccines offer considerable protection for patients after the first dose.
“This measure will have the greatest impact on reducing mortality, severe disease, and hospitalisations, helping to protect the
NHS and save lives.”
When asked about this concern, a Department of Health and Social Care spokesperson did not directly answer the question,
saying rather that it was “vital we do everything we can to quickly and safely protect as many vulnerable people as possible from
this virus” and that data from manufacturers showed considerable protection for patients after the first dose.
The British Society for Immunology has called on the government’s advisory committee on vaccines to make the “full evidence for
decisions around covid-19 vaccines available immediately” to build public trust. “Having access to the evidence and rationale
behind the public health decisions taken is important,” it said in a statement.15 “The government have confirmed that openness
and transparency are vital. The British Society for Immunology will continue to monitor and advocate for this.”
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References
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Wecontent/uploads/sites/52/2020/12/C0994-System-letter-COVID-19-vaccination-deployment-planning-30-December-2020.pdf.
and our partners store and/or access information on a device, such as unique IDs in cookies to process
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at any time in the privacy policy page. These choices will be signaled to our
partners and will not affect browsing data. Cookie policy
uk-covid-19-vaccination-programmes/letter-to-the-profession-from-the-uk-chief-medical-officers-regarding-the-uk-covid-19-vaccination-
programmes.
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7. EU says interval between Pfizer vaccine doses should be respected. Reuters. 4 Jan 2020. https://www.reuters.com/article/us-health-
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11. Medicines and Healthcare Products Regulatory Agency. Information for healthcare professionals on covid-19 vaccine AstraZeneca. 5 Jan
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13. Henley J, Oltermann P, Willsher K. Germany and Denmark consider delaying second covid vaccine dose. Guardian. 4 Jan 2020.
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14. Branswell H. Britain takes a gamble with Covid-19 vaccines, upping the stakes for the rest of us. Stat2021.
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15. British Society for Immunology. Statement on covid-19 vaccine dosing schedules. https://www.immunology.org/policy-and-public-
affairs/briefings-and-position-statements/COVID-19-vaccine-dosing-schedules.
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