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In view of the increase in coronavirus cases, some European countries are considering the possibility of changing course and joining the United Kingdom in vaccinating as many people as possible with just one dose, instead of the two administered during clinical trials so far.
This problem has been in the air since December 30, when the United Kingdom announced its decision to postpone second doses for up to 12 weeks, when it approved the Oxford / AstraZeneca vaccine for emergency use. The option also applies to the BioNTech / Pfizer jab.
Just this week, Denmark announced its decision to delay the second dose of both Pfizer and Moderna jabs by up to six weeks. The German health ministry also confirmed the possibility of expanding vaccination coverage through similar delays between doses.
Meanwhile, the US federal government is in talks with Moderna about halving the recommended dose of the injection to speed up immunization efforts.
Scientists are divided. Some argue that delaying it can cause more mutations in the virus and make the injection ineffective. Others question whether recipients will be more vulnerable, pointing out that allowing longer intervals between doses has not been tested correctly.
The pro-delay field argues that an immediate broader level of protection, although slightly weaker, is better than providing stronger protection for half the number of people. UK Deputy Chief Medical Officer Jonathan Van-Tam emphasized this point in Mail on Sunday, saying that maximizing coverage with the first dose “will save lives”.
Belgium’s leading epidemiologist, Pierre Van Damme, also supports the idea of a suspended dosage. Speaking to VRT broadcaster last week, he said the strategy would quickly provide protection to more people and “herd immunity would increase at a much faster rate”. (Belgium’s Minister of Health, Frank Vandenbroucke, asked the vaccination task force to examine the possibility of delays between doses, but has not yet made a statement, with his spokesman warning that there is still insufficient evidence for the change .)
With a reduced supply of vaccines and new variants of the UK and South African coronavirus causing alarm – compounded by overburdened health systems – some politicians are now on the side of the latter field.
The problem: although the UK approach has been developed and supported by many public health scientists, it lacks the rigor of the controlled tests that the UK is so well versed in.
Not fully tested
The idea of vaccinating as many people as possible with the Oxford / AstraZeneca vaccine before being approved for emergency use was first put forward by former Prime Minister Tony Blair in early November. He was quickly rejected by doctors and scientists on the grounds that he would override controlled clinical trials already underway for these treatments. These studies end up eliminating therapeutic winners (dexamethasone) from losers (hydroxychloroquine).
The debate changed even more this week, when the British Society for Immunology gave the thumbs-up on Monday. Although their statement puts “maximum value in an evidence-based approach to medical decisions”, they called for a “pragmatic approach in the short term”, given the “unprecedented situation”. The Society supported the postponement of the two-dose scheme – provided that the government develops a “robust immunological monitoring program”.
Sheila Bird, a former program leader at the University of Cambridge’s MRC Biostatistics Unit, took it a step further. In an emailed statement on Monday, she asked the UK to randomize the standard and late dosing schedules to compare the effectiveness of both approaches.
“The tests would be good for all these variations, although the data we have shows very good protection from a dose of AstraZeneca or Pfizer [vaccines]… The speed and breadth of vaccination are crucial to success, “said Professor John Bell of Oxford University, who is also a member of the UK vaccination task force, via email.
Single shot data
In their defense of postponing doses, medical directors in the United Kingdom pointed to data showing that the effectiveness of the short-term vaccine since the first dose is about 90% with the BioNTech / Pfizer vaccine and about 70% with the vaccine Oxford / AstraZeneca. The second dose is likely to be “very important for the duration of protection,” they said in a joint letter dated December 31.
Some scientists, however, remain concerned that efficacy may decline beyond the indicated three and four week periods for the second doses of the Pfizer and AstraZeneca vaccines, respectively.
British Society for Immunology data on the BioNTech / Pfizer vaccine, for example, show that antibodies and T cells are neutralized more effectively after the second dose. The society also notes that “likewise, the Oxford / AstraZeneca vaccine shows substantial immunological differences after the second 28-day dose”.
They concluded, however, that delaying a second dose by eight weeks “probably would not have a negative effect on the overall immune response after the booster.”
Peter English, former editor of Vaccines in Practice and former chairman of the British Medical Association’s Committee on Public Health Medicine, also exposed the case of delays. In an opinion piece on Monday, he wrote that decades of experience with other vaccines have shown that, at the very least, “increasing the range will increase the quality of the booster response.”
Approved single dose arriving?
With Johnson & Johnson investigating the issue in a large clinical trial, more data on the effectiveness of a single dose and the duration of protection is likely to be released later this month.
Like the Oxford / AstraZeneca jab, the J&J vaccine is based on adenovirus viral vector technology. He uses a modified cold virus to transport information to cells, instructing them to produce the protein spike antigen to build an immune response.
J&J, which has experience with pandemic vaccination after the successful approval and launch of its Ebola vaccine, said in November that while a single dose vaccine “has significant benefits, especially in a pandemic scenario,” the The company’s vaccine program is also testing two doses in a separate trial.
The first unpublished results from a first-phase clinical trial showed that a single dose is effective in generating sufficient antibodies in 98 percent of patients after 29 days, the company said.
With pending positive results, the U.S. drugmaker plans to apply for global licenses with data that support the single-dose scheme. The European Medicines Agency expects to reach a decision in March.
Final obstacle
The UK approach allows for the off-label use of the Pfizer and AstraZeneca vaccines, which means that these jabs can be administered outside their licensed indication without consequences. This is possible due to the instructions of the Joint Committee on Vaccination and Immunization, which offers protection against reprisals.
The same does not apply in other parts of Europe, where countries will use EMA approved vaccines.
“I don’t think healthcare professionals … in the EU would endorse or otherwise be inclined to promote any kind of off-label use,” said Vincenzo Salvatore, Bonellei Erede’s lawyer and former EMA legal director.
“Any change to [administration] it would require a variation in marketing authorization, “said the EMA, as reported by Reuters,” as well as more clinical data to support such a change. Otherwise, it would be considered ‘off-label use’. “
Vaccine manufacturers have also defended clinically approved indications.
“Our Phase 3 clinical trial and the US Emergency Use Authorization are associated with 100ug in two doses, 28 days apart,” said a spokeswoman for Moderna in an email on the subject of half-doses. In the USA
BioNTech echoed this sentiment in the FT, reiterating that there are no data to support the administration of two doses of its vaccine administered more than 21 days apart.
English, who is also a consultant in communicable disease control in the UK, said the vaccine committee’s benefit is that it “sees the population and needs in general”. It includes decades of knowledge about vaccines, the immune system and how they interact – “not just according to the tests that were done to obtain the license”.
He also warned of the deadly risk of limiting the factors that affect these decisions.
“People are dividing themselves between those who want direct, explicit and restricted empirical evidence and those who want to extract extrapolation from indirect evidence,” he said. “The point is that lives can be lost if we wait for the direct evidence.”
Charlie Cooper, Hans von der Burchard and Camille Gijs contributed reporting.
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