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Faced with rising coronavirus cases, some European countries are considering changing course and joining the UK to vaccinate as many people as possible with just one dose instead of the two given so far in clinical trials.
This has been an issue since December 30, when the UK announced its decision to delay the second dose for up to 12 weeks when it approved the Oxford / AstraZeneca emergency vaccine. The switch also applied to the BioNTech / Pfizer prod.
Just this week, Denmark announced its decision to delay the second dose of both the Pfizer and upcoming Moderna jabs for up to six weeks. The German Ministry of Health has also confirmed that it is investigating an extension of vaccination coverage due to comparable delays between doses.
Meanwhile, the US federal government is in talks with Moderna about halving the recommended dose of the shot to speed up immunization efforts.
Scientists are divided. Some argue that delay can cause further virus mutations and make recording ineffective. Others question whether recipients will be left more vulnerable, pointing out that allowing greater differences between doses has not been properly tested.
The pro-delay camp argues that an immediate level of broader, if slightly weaker, protection is better than stronger protection for half the people. Jonathan Van-Tam, deputy chief of medical services, highlighted this point in the Mail Sunday, saying that maximizing coverage with the first dose “will save lives.”
Belgium’s leading epidemiologist, Pierre Van Damme, also supports the idea of interrupted dosing. He told broadcaster VRT last week that the strategy would soon provide more people with protection and that “the herd’s immunity would grow much faster.” (Belgian Health Minister Frank Vandenbroucke has asked the vaccine task force to investigate the possibility of delays between doses, but has not yet issued a statement, with his spokesperson warning that there is still not enough evidence for the move.)
With vaccine stocks squeezed out and new British and South African coronavirus variants sounding the alarm – exacerbated by overburdened health systems – some politicians are now sided with the latter camp.
The catch: While the UK’s approach has been developed and supported by many public health scientists, it lacks the rigor of controlled testing 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 it was approved for emergency use was first pitched by former Prime Minister Tony Blair in early November. It was quickly rejected by doctors and scientists as it would thwart the controlled clinical trials that were already underway for these treatments. Such studies eventually removed therapeutic winners (dexamethasone) from losers (hydroxychloroquine).
The debate shifted further this week when the British Society for Immunology failed its hand on Monday. While their statement “placed the greatest value on an evidence-based approach to medical decisions”, they called for a “short-term pragmatic approach” given the “unprecedented situation”. The Society supported the delayed two-dose schedule – provided the government develop a “robust immune monitoring program.”
Sheila Bird, former program leader at Cambridge University’s MRC Biostatistics Unit, went one step further. In an e-mail statement on Monday, she called on the UK to randomize standard and delayed dosing schedules to compare the effectiveness of both approaches.
“Trials would be good for all of these variations, although the data we have shows very good protection against a single dose of AstraZeneca or Pfizer. [vaccines]… The speed and scope of vaccination is critical to success, ”said Professor John Bell of the University of Oxford, who is also a member of the UK Vaccine Task Force, in an email.
Single shot data
In their defense of delaying doses, the UK’s Chief Medical Officers pointed to data showing that the vaccine’s short-term efficacy from the first dose is about 90 percent with the BioNTech / Pfizer vaccine and about 70 percent with the Oxford / AstraZeneca vaccine. The second dose is likely to be “very important for the duration of protection,” they said in a December 31 joint letter.
However, some scientists remain concerned about whether the effectiveness could decline after the stated three- and four-week periods for second doses of the Pfizer and AstraZeneca vaccines, respectively.
For example, data from the British Society for Immunology on the BioNTech / Pfizer vaccine shows that antibodies and T cells are more effectively neutralized after the second dose. The association also notes that “similarly, the Oxford / AstraZeneca vaccine shows significant immunological differences after the second dose at 28 days.”
However, they concluded that delaying a second dose for eight weeks is unlikely to “have a negative effect on the overall immune response after the boost.”
Peter English, former editor of the journal Vaccines in Practice and former chairman of the British Medical Association’s Public Health Medicine Committee, also outlined the arguments for delays. In an opinion piece on Monday, he wrote that decades of experience with other vaccines have shown that “increasing the interval will improve the quality of the booster response.”
Approved single dose is coming?
Now that Johnson & Johnson has investigated the issue in a major clinical trial, more data on the efficacy of a single dose and duration of protection is likely to emerge by the end of the month.
Like the Oxford / AstraZeneca shot, the J&J vaccine is based on adenovirus viral vector technology. This uses a modified cold virus to bring information to the cells and tell them to make the spike protein antigen to build an immune response.
J&J, which has experience in pandemic vaccination following the successful approval and launch of its Ebola vaccine, said in November that while a single dose vaccine would have “significant benefits, especially in a pandemic environment,” the company’s vaccine program also included two test. doses in a separate trial.
Unpublished early results of 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.
Pending positive results, the US drug company plans to file global licenses with data supporting the single-dose schedule. The European Medicines Agency hopes to reach a decision in March.
Last hurdle
The UK approach allows for the off-label use of both the Pfizer and AstraZeneca vaccines, meaning that these injections can be administered without consequences outside the approved indication. This is possible thanks to instructions from the Joint Committee for Vaccination and Vaccination, which offers protection against retaliation.
The same is not true elsewhere in 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, a lawyer at Bonellei Erede and former chief counsel at the EMA.
Any change in [administration] would require a change to the 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 US emergency use clearance have been associated with 100 µg in two doses 28 days apart,” said a Moderna spokesperson in an email on the subject of US half doses.
BioNTech echoed this sentiment in the FT, reiterating that no data exists to support the administration of two doses of its vaccine given for longer than 21 days apart.
Engels, who is also an adviser on communicable disease control in the UK, said the benefit of the vaccine committee is that it “sees the population and needs in the round”. It contains decades of knowledge about vaccines, the immune system and how they interact – “not just according to tests done to get the license.”
He also warned of the deadly risk of limiting the factors influencing these decisions.
“People divide into those who want explicit, narrow-minded, direct empirical evidence and those who are willing to bring in extrapolation from circumstantial evidence,” he said. “The problem is, lives can be lost if we wait for the scary direct evidence.”
Charlie Cooper, Hans von der Burchard and Camille Gijs contributed to the report.
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