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expert reaction to comments made by Tony Blair suggesting we should consider using all available vaccine doses in January as first doses, rather than keeping some back for use as second doses

Tony Blair has made comments suggesting we should consider using all available vaccine doses in January as first doses, rather than keeping some back for use as second doses


Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“This is not a simple question.  No trials of the Pfizer/BioNTech vaccine were done using a single dose as the intended procedure so the amount of data on efficacy of a single dose is limited.

“The FDA in their briefing document (which is a more reliable source on the details than the New England Journal of Medicine) on the assessment of the Pfizer/BioNTech vaccine say: “Among all participants (regardless of evidence of infection before or during the vaccination regimen), 50 cases of COVID-19 occurred after Dose 1 in the BNT162b2 group compared with 275 cases in the placebo group, indicating an estimated VE of 82% (95% CI: 75.6%, 86.9%) against confirmed COVID-19 occurring after Dose 1, with VE of 52.4% (95% CI: 29.5%, 68.4%) between Dose 1 and Dose 2. The efficacy observed after Dose 1 and before Dose 2, from a post-hoc analysis, cannot support a conclusion on the efficacy of a single dose of the vaccine, because the time of observation is limited by the fact that most of the participants received a second dose after three weeks. The trial did not have a single-dose arm to make an adequate comparison.”

“What is clear is that there is evidence of efficacy in the short term, and it seems likely that the efficacy will not decline notably.  This efficacy is clearly nearer 80% than 90% and could be quite a bit lower but is still good.

“At the moment, as far as one can tell, the limiting factor is not dose availability but the resources for carrying out the vaccinations.  These resources are personnel, logistics of delivery and storage.  Cold chain requirements are making it difficult to arrange for vaccination within care homes.  If availability of doses becomes the limiting factor, it could well be that the population overall is better served by delaying the second dose.  The same may be true if personnel resources are limiting the number of vaccinations that can occur.

“The Oxford/Astra Zeneca vaccine was originally intended to have evaluation of a single dose, but the early results from the blood tests (immunogenicity) suggested that a two-dose regimen was much better.  If the Oxford/Astra Zeneca vaccine receives an authorisation in the UK by early January, large numbers of doses of this vaccine will become available for use so dose availability should no longer be a key factor.  However, resources for carrying out vaccinations may still be a problem.  At that point it would certainly be worth re-visiting the strategy of giving everyone the dose at the approved time – 21 days after the first dose for the Pfizer/BioNTech vaccine.

“There is a legal difficulty in that the Pfizer/BioNTech vaccine authorisation is for two doses 21 days apart and not for a single dose.  If JCVI were to go against that authorisation it may create difficulties in legal terms but this is a pandemic.

“The full efficacy is not reached until at least 7 days after the second dose.  However, the evidence we have for vaccines in general, though not carefully tested for these vaccines, is that delaying a second dose will not result in reduced long-term efficacy.  Those who do not receive a second dose will not be at higher risk in the long term, but certainly are more at risk in the period between when they should receive the second dose and when they actually receive it.

“Vaccines are not drugs; it is not a medicine like an antibiotic where delays in getting second (or subsequent) doses means that that the drug levels decline and benefit disappears.  With a vaccine the benefit of the single dose is expected to be retained while awaiting a second dose, it is simply that there will be a delay in achieving full benefit.

“Balancing benefits between individuals or ensuring that as many individuals as possible get some benefit and hence that the population has an overall greater protection is not easy.  It is best to rely on careful modelling and I have no doubt that JCVI is very aware of the issues.

“This is not a question with a simple answer.”


Prof Peter Openshaw, past president of the British Society for Immunology, and Professor of Experimental Medicine at Imperial College London, said:

“Any move to give just one dose of vaccines that have been tested and licenced in a 2-dose regimen would be cutting across normal practice, but make good sense.  Vaccines that prove more effective than expected might logically be tested in a lower dose or in a reduced dose regimen, but the effects would need to be closely monitored.  It does make sense immunologically that a highly effective vaccine might only need one dose, but the durability of the protection is unpredictable.  A booster might be needed subsequently to enhance responses and make them last longer.

“It is also compelling that a single dose regimen should be assessed given the limited supply of vaccines.  The published data show that almost complete protection is evident within 12-14 days of the first dose of the mRNA (Moderna or BioNTech) vaccines.  It therefore seems that just one dose will confer adequate protection, at least for a limited period.  The booster might not need to be by administration of the same vaccine, and there are arguments that boosting with a different vaccine might be advantageous.

“The vaccine that prevents cervical cancer, the HPV vaccine, was initially a 3 dose regimen.  It is so remarkably effective in preventing papilloma virus infection that this has now become a two dose regimen.  A reduction in doses is therefore not unprecedented, and has been used with childhood flu vaccine when supplies were limited.

“Moving to a single dose regimen seems a sensible tactic in terms of getting as many people as possible protected now, but the effect needs to be carefully monitored and plans put in place for later boosting of responses if necessary.  For now, people should continue to follow advice from those responsible for their care.”


Dr Andrew Garrett, Executive Vice President of Scientific Operations, ICON, said:

“Dosing is determined by the approved labelling of a vaccine, and this has been, and will be, determined in the UK  by the MHRA on the basis of the evidence submitted to them.  Any subsequent change of dosing would be experimental therefore.  If the MHRA, in association with the Sponsor, determined that the accumulating evidence, including the immunological response data, supported the possibility of an effective one dose regimen, then one option would be to initiate a large clinical trial within the general roll-out program.  This would be akin to the UK’s Recovery trial that studied approved drugs, in the first instance, for the treatment of COVID-19.  So far over 20,000 patients have been included in the Recovery trial.  Specific centers could randomize consenting individuals to one or two doses of vaccine using a simplified and pragmatic protocol that collected key information only (including via patient records).  Using this approach, for every four participants randomized, two doses of the vaccine would be freed up for another person.  If a 2:1 ratio were used then for every three participants randomized, two doses would be freed up.  Other vaccines (and combinations) could be added subsequently using this platform design.  There remain many unanswered questions, and new questions will emerge, so it will be important for the UK to create an experimental framework to continue to gather objective vaccine evidence to support public health.  As Tony Blair states “we need the best data system available in the world and we need it now”.”

Interview with Tony Blair on the BBC Radio 4 Today Programme this morning; skip to 1:51:43 at this link:


All our previous output on this subject can be seen at this weblink:


Declared interests

Prof Stephen Evans: “No conflicts of interest.  I am funded (one day per week) by LSHTM.  They get funding from various companies, including Astra Zeneca and GSK but I am not funded by them, I have no involvement in obtaining funding from them and I am not an investigator on any grants obtained from them.  I am the statistician to the ‘meta-Data Safety and Monitoring Board’ for CEPI.  I am paid for my attendance at those meetings and will be paid expenses for travel if that occurs.”

Prof Peter Openshaw: “I have been on an advisory board, Chaired a Satellite meeting and delivered a Keynote sponsored for Janssen/J&J at ESWI conference. Fees to Imperial.

I have been on scientific advisory boards for Nestle and for Pfizer in relation to immunity to viruses, but not on Covid-19. Fees to Imperial.

I am the Imperial College lead investigator on the EMINENT consortium which receives £8m from the MRC and matched funds from GSK. This funds the INFLAMMAGE programme, which involves RSV challenge of older adult volunteers.”

Dr Andrew Garrett: “I am employed by ICON which is a Contract Research Organization .  ICON provides pharmaceutical services to the pharmaceutical and biotechnology industries. ICON conducts clinical trials on behalf of Sponsors, including vaccine trials.”

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