To delay people’s second dose of the Covid-19 vaccine, or not to delay it? It seems there’s no obvious answer to that question.

Two vaccines are already being distributed in the UK – the Pfizer-BioNTech vaccine and the Oxford/AstraZeneca vaccine both require two doses for maximum protection against the virus, spaced three or four weeks apart. Meanwhile, a third vaccine by Moderna has been approved, with supplies scheduled to arrive in spring.

However, due to the current very high transmission rates in the UK, the government has said that rather than aiming to give a smaller number of people two doses of the vaccine as initially set out, vaccinating a greater number of people with a single dose first – and therefore delaying the second dose – will prevent more deaths and hospitalisations.

The decision was made based on advice issued by the Joint Committee on Vaccination and Immunisation (JCVI) at the end of December which claimed short-term vaccine efficacy from the first dose of the Pfizer-BioNTech vaccine is calculated at around 90%, while for the AstraZeneca vaccine it’s calculated at around 70%. JCVI has the backing of the chief medical officers in the UK.

“The second dose is still important to provide longer lasting protection and is expected to be as or more effective when delivered at an interval of 12 weeks from the first dose,” reads the guidance. 

The change in guidance is believed to be due to vaccine shortages caused by global demand, and the recent increased transmission of the virus in the UK. In parts of England, it’s thought one in 50 people have Covid, while in London the figure is nearer one in 30.

There has already been a strong response to the proposals.

The World Health Organisation (WHO) has advised the second dose of the vaccine should only be delayed by up to six weeks.

Meanwhile some GP surgeries in England have decided not to cancel appointments for patients scheduled to have their second dose of the vaccine three weeks after the first, the Independent reported.

In the US, the Food and Drug Administration (FDA) said any changes to the dosing or schedules of these vaccines would be “premature and not rooted solidly” in the available evidence. “Without appropriate data supporting such changes in vaccine administration, we run a significant risk of placing public health at risk, undermining the historic vaccination efforts to protect the population from Covid-19,” it said in a statement on January 4.

What do health experts think about delays?

Dr Stephen Griffin, associate professor in the School of Medicine at the University of Leeds, is particularly concerned about plans to alter the Pfizer vaccine’s dosing schedule. While the data supporting the Pfizer vaccine robustly supports having two doses given 21 days apart for the vast majority of the patients involved in the phase III trial, the data for the Oxford/AstraZeneca vaccine is “more nuanced and broader”, he explains.

The UK Medicines and Healthcare products Regulatory Agency (MHRA) provided authorisation for emergency supply of AstraZeneca’s vaccine and recommends two doses administered with an interval of between four and 12 weeks, which fits with the altered criteria. According to AstraZeneca, this regimen was shown in clinical trials to be safe and effective at preventing symptomatic Covid-19, with no severe cases and no hospitalisations more than 14 days after the second dose.

“Each vaccine brings different benefits,” says Dr Griffin, “with Pfizer being highly effective within a somewhat inflexible framework, whereas the greater breadth of conditions within the AstraZeneca trial revealed the apparent increase in efficacy where doses were spaced further apart.

“Given the differences in both the nature of these vaccines and the way in which trials were delivered, it is a concern that aspects deemed favourable for one vaccine should now also be applied to the other.”

The changes would mean using the Pfizer vaccine ‘off-label’, Dr Griffin explains, which meaning not following the exact instructions that have been approved. “The company has understandably distanced itself from this notion”, he says. 

Pfizer told HuffPost UK in a statement that recommendations on alternative dosing regimens reside with health authorities and may include recommendations due to public health principles.

But as a biopharmaceutical company working in a highly regulated industry, its position is supported by the label and indication agreed upon with regulators, and informed by data from its Phase 3 study.

“Pfizer and BioNTech’s Phase 3 study for the Covid-19 vaccine was designed to evaluate the vaccine’s safety and efficacy following a 2-dose schedule, separated by 21 days,” says Pfizer’s spokesperson.

The safety and efficacy of the vaccine has not been evaluated on other dosing schedules. “The UK is notably the only country currently considering this path,” says Dr Griffin. “Given the tremendous effort and investment required to mount clinical trials on this scale, it feels unwise to alter the Pfizer protocol – put simply, if it ain’t broke, don’t fix it.”

But Professor Stephen Evans, an expert in pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, acknowledges that there isn’t an easy solution to the current “crisis situation”.

“This is not a simple problem. The idea that there is a definite clear-cut answer is not true because respected scientists differ in their views,” he says. “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.

“It is safest and most cautious to use the vaccines in the exact conditions reflecting the trials. However, this will never be possible in the real world and the question is how much moving outside the exact conditions is acceptable.”

Prof Evans points out that pharmaceutical companies are constrained by law and must only make claims that are reflected in the authorisation documents set out by regulatory authorities. But clinicians and health authorities have to take the circumstances they are dealing with into account.

“We have a crisis situation in the UK with a new variant spreading rapidly,” he says, “and as has become clear to everyone during 2020, delays cost lives.”

Vaccinating only half of a vulnerable population will lead to a notable increase in cases of Covid-19, says Prof Evans. “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,” he adds. 

The British Society for Immunology, a professional body representing scientists and clinicians who study the immune system, has said that while it would prefer the original dosing schedules tested in the trials to be used, it recognises a pragmatic approach in the short-term is needed – which is why it accepts the rationale for the change in dosing schedule for the Oxford/AstraZeneca and Pfizer/BioNTech vaccines.

“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 effect on the overall immune response post-boost,” the society said in a statement.

“We also would not expect any specific safety issues to arise for the individual due to delaying the second dose, other than an increased potential risk of disease during the extended period due to lowered protection.”

So what happens now?

People will receive the first dose but may have to wait up to 12 weeks to receive their second. This doesn’t mean they won’t receive the second dose at all, however. Having two doses offers the highest level of protection available.

You can still catch Covid-19 after having your first dose, although your risk of becoming seriously ill is lower. With this in mind it’s important to remember to regularly wash your hands, wear a mask in public, and socially distance. People who are shielding should continue to do so even after having the vaccine. 

Scientists, including the British Society for Immunology, have now called for a programme to monitor how the delayed dosing impacts efficacy of both vaccines, “with rapid modification of dosing schedules as appropriate”.