GP and aesthetic practitioner Dr Ravi Brar explains what the data shows about the second-dose scheduling
We are all fully aware of the devastation that coronavirus disease 2019 (COVID-19) has caused and continues to do so, but with effective vaccines now being approved, it is the closest that we have been to seeing a light at the end of the tunnel.
We are lucky to now have three vaccines approved for the UK. Pfizer-BioNTech and Moderna are an entirely new kind of vaccine compared to the Oxford-AstraZeneca.1 The Oxford-AstraZeneca vaccine makes use of an inactive cold virus to produce the coronavirus spike protein. The other two carry messenger RNA (mRNA) which instructs the body’s own cells to build the spike protein. This in turn stimulates the immune system to produce antibodies and activate T-cells which prepare the immune system to respond to any future exposure to the COVID-19 virus.1
In December, my colleagues and I started to receive in-depth material when the first vaccine (Pfizer-BioNTech) was approved. This included the appropriate training to ensure we were ready to start rolling out the programme as soon as the first packages of the vaccine hit our vaccination centre fridges. My administration team had started to book in patients, not only for their first dose, but they were also giving preliminary dates for the second dose. At that point, it was three to four weeks after their first jab. However, the announcement in late December changed this protocol for both the Oxford-AstraZeneca and the Pfizer-BioNTech vaccine. The advice is now that the second dose of both vaccines should be given 12 weeks after the first.
There has been much discussion as to why this change has occurred. One reason being that this way, it would help vaccinate more people. So, let’s have a look at the data.
Polack et al. (2021) published a paper in the New England Journal looking at the safety and efficacy of the Pfizer-BioNTech vaccine.2 The clinical trial vaccinated 43,448 participants (21,720 injected with the vaccine and 21,728 with a placebo) across six countries. At the data collection cut-off date there were 37,706 participants.2 A key exclusion criterion from the study was immunosuppression (those on medication or secondary to an immunosuppressive condition).2
Participants received their second dose 21 days after the first. The study showed that 95% protection was achieved seven days after the second dose.2 The group also reported that the efficacy between the first and second dose was 52%.2,3 We should remember that the study was not designed to look at single-dose vaccination and this figure included COVID-19 infections that occurred shortly after the first dose. This is important as the study noted that the vaccinated group started to diverge from the placebo after day 10, suggesting that is when the immunity starts to build.2,3Therefore, true efficacy of a single dose of vaccination should be assessed from a period after 10 days, which the study did not report.
The Joint Committee on Vaccination and Immunisations (JCVI), a body that advises UK health departments on immunisation, had a closer look at the data and suggested that a reasonable interval to assess for single-dose vaccination efficacy would be from day 14 onwards.3 This shows an efficacy of 90%, a figure much higher than the 52% reported in the study by Polack et al. (2021).3 Due to this tremendous protection after a single dose, the JCVI advised that the maximum interval between the first and second dose should be 12 weeks.3 There is still lack of evidence to show how long this immunity lasts after 21 days.
Data has been collected from a clinical trial that started in April 2020. It included just under 24,000 participants in the UK, Brazil and South Africa.1,4 The participants were randomised and received either the vaccine or a placebo in the form of a meningococcal vaccine or saline. Studies are still ongoing in the US, Kenya, Japan and India.1,4
Unlike the Pfizer-BioNTech vaccine,there is data from the Oxford-AstraZeneca vaccine study for different vaccination intervals.1,4
The study reported single-dose vaccination efficacy was 70%, and greater protection from severe disease from 22 days after the first dose.1,3,4 This highlights that a longer interval allowed for a greater immune response, hence a single dose of the Oxford-AstraZenecawill provide high short-term protection against severe disease. This again led to JCVI advising that the maximum interval between the first and second dose should be 12 weeks.3
The most recent vaccine that has been approved is the Moderna. Data was collected from a randomised study that included 30,351 participants, with vaccinations taking place in 99 sites across the US.5 The data showed an efficacy of 94% with two doses given 28 daysapart.3,5 The Moderna vaccine has a single-dose efficacy of 92.1% from day 15 post-jab,3 however the data is limited when looking at protection provided after 28 days from a single dose.
We are still to receive more information when this vaccine will be available, and how it will be deployed amongst the two other vaccines in the UK.
The JCVI released a statement highlighting their considered options to increase the impact of the vaccination programme in the short term.3 The advice given was to help maximise protection within the population. They concluded that with the current situation, with increasing cases, there is more benefit in vaccinating more of the population with a single dose than vaccinating a smaller number with two doses. This, in turn, will help control the spread of the virus and hope to lower hospitalisations.
The data summarised above should provide patients with reassurance that single dose of any of the available vaccines does provide effective protection after two weeks. However, it should be stressed that getting the vaccine should not mean we stop following the COVID-19 precautions. Finally, the second dose is important to ensure more durable and prolonged protection, with studies continuing to ascertain the duration of this immunity.
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