MSCOVID#19 The immunologists speak


British Society for Immunology statement on COVID-19 vaccine dosing schedules

As the professional body representing scientists and clinicians who study the immune system, the British Society for Immunology places the utmost value on an evidence-based approach to medical decisions. Our priority is always to see that COVID-19 vaccines are rolled out in a manner that maximises safety and protection while minimising serious disease. However, we also recognise that the UK now faces an unprecedented situation. We have an extremely challenging few months ahead with high levels of SARS-CoV-2 circulating through our communities together with the emergence of the new, more transmissible variant resulting in extra pressure on healthcare services. 

Given this, although we would prefer the original dosing schedules tested in the trials to be used clinically, we recognise that a pragmatic approach in the short-term is needed, and accept the rationale for the change in dosing schedule for the Oxford/AstraZeneca and for the Pfizer/BioNTech vaccine that has been recommended by the Joint Committee on Vaccination and Immunisation (JCVI). Our reasons for this can be summarised as follows:

  1. Evidence based decisions. For the Pfizer/BioNTech vaccine, the immunology from preclinical to phase 2 trials shows that better neutralising antibodies and T cell levels are achieved after the second dose.1,2,3 Similarly, the Oxford/AstraZeneca vaccine shows substantial immunological differences after the second dose at 28 days.4 The current government policy is that the second dose should be delayed from 3 or 4 weeks to 12 weeks maximum, not that people should not receive the second dose. The phase 2/3 trial data show how many people are protected from symptomatic disease after the first dose by the Pfizer/BioNTech BNT162b2 vaccine.3,5 The exact relationship between the immunology and the disease protection data is uncertain but the Chief Medical Officers and the JCVI have noted that, by taking all relevant issues and data into consideration, more people can be protected from symptomatic disease in the short-term by extending the second dose up to 12 weeks. There is also some evidence from the Oxford/AstraZeneca vaccine that this approach may be beneficial.6  There is no suggestion by the government that the second ‘booster’ dose should be extended any longer than 12 weeks. There is no current evidence that either of the two approved vaccines can prevent infection by the virus (rather they stop disease), so any concerns that delaying a second dose would have adverse effects on virus transmission remain hypothetical. Close monitoring of the vaccinated population will now be needed in order to garner further evidence.
  2. Expert opinion. 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. 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.
  3. Pragmatism. The SARS-CoV-2 virus continues to spread despite the societal restrictions introduced so far. This increase in case number means our hospitals are experiencing very high admission numbers, leading to pressure on our healthcare system. With the number of cases and deaths continuing to increase at a significant rate, we need to protect as many vulnerable people as possible from severe COVID-19 disease in the short-term. Modelling data has shown that vaccination has by far the largest chance of reducing the disease burden and death rate compared with other measures.7 Any risks from actions taken now must be balanced against risks of actions not taken. Concerns over hypothetical consequences of putting the virus under pressure from non-sterilising vaccine regimes have to be balanced against a view of what we would face through the virus spreading at the current rate in our communities.  

Given this change in dosing schedule deviates from our preference of a strict evidence-based approach, we have called on the government to ensure the following is implemented:

  1. A robust programme of immune monitoring to assess how altering the dosing schedule impacts efficacy of both the Pfizer/BioNTech and Oxford/AstraZeneca vaccines, with rapid modification of dosing schedules as appropriate. This monitoring should include studies from a number of sources including the vaccine development teams but also monitoring from Public Health England and the devolved nations to learn as much as we can about how the altered dosing schedule affects immune responses in the medium and longer term. We have been assured by the government that this monitoring is in place and will be conducted. The British Society for Immunology will track progress and advocate for data to be made available for analysis and scrutiny.
  2. A high-profile, multifaceted engagement programme to build public understanding and confidence in COVID-19 vaccination.  This should include two-way engagement of actively listening and responding to the public’s questions around vaccination and taking account of how these questions may differ between diverse communities. Government have accepted that this is a vital part of the vaccination programme and in addition to their own planned activities, welcome the role that members of the British Society for Immunology can play in engaging with the public to build understanding and confidence.
  3. Strong and clear messaging to the public that the highest level of protection is only gained through two doses of the vaccine.  It is imperative that we make it clear to the public that, although the dosing schedule has changed, two doses are still needed by all. With a greater amount of time between doses we now risk a larger proportion of those receiving a first dose not returning for a second dose thereby compromising the protection levels in the most vulnerable in society. We have been assured by Government that this is a priority and that the policy is to deliver the second dose with a maximum of 12 weeks.
  4. The JCVI to make the full evidence for decisions around COVID-19 vaccines available immediately upon announcements being made to aid public understanding. An open and transparent approach is required to build public trust, and thus having access to the evidence and rationale behind the public health decisions taken is important. The government have confirmed that openness and transparency is vital. The British Society for Immunology will continue to monitor and advocate for this. JCVI minutes


  1. Mulligan et al. 2020 Phase 1/2 Study to describe the safety and immunogenicity of a COVID-19 RNA vaccine candidate (BNT162b1) in adults 18 to 55 years of age: interim report. medRxiv, doi: 10.1101/2020.06.30.20142570
  2. Sahin et al. 2020 BNT162b2 induces SARS-CoV-2-neutralising antibodies and T cells in humans. medRxiv, doi: 10.1101/2020.12.09.20245175
  3. FDA briefing document. 10 December 2020. Pfizer-BioNTech COVID-19 Vaccine.
  4. Ramasamy et al. 2020 Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. The Lancet 396 P1979–P1993 doi: 10.1016/S0140-6736(20)32466-1
  5. Polack et al. 2020. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. New England Journal of Medicine 383 2603–2615 doi: 10.1056/NEJMoa2034577
  6. Voysey et al. 2020. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. The Lancet doi: 10.1016/S0140-6736(20)32661-1
  7. Davies et al. 2020. Estimated transmissibility and severity of novel SARS-CoV-2 Variant of Concern 202012/01 in England. medRxiv doi: 10.1101/2020.12.24.20248822

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  • Thanks for sharing this. Do you think more will be said about adapting the dosing schedule back to the original 21 days to assist pwMS on ocrelizumab in timing the vaccination to elicit the best response?

      • You might recall that I was offered the vaccine today but my ocrelizumab is booked for tomorrow. I decided to decline the vaccination and have my infusion as planned. I’ve since found out from the Trust’s Vaccination Lead that there is wiggle room for the dosing schedule for clinical reasons. I’ve to contact her once I’ve the green light to go ahead. My original thinking was to leave at least 6 weeks from my infusion but according to the Veloce study 12 weeks or more is best.

        What’s the current thinking? I don’t want to wait too long so don’t get the vaccine as soon as possible but would prefer to elicit the most effective response. I’ve been on ocrelizumab since April 2019 and tomorrow will be my 3rd full dose.

        • Dear Debbie
          The current thinking is not based on knowledge as you say the VELOCE study was 12 weeks. We (neuros) have a discussion tomorrow to determine what the options are and will then have another discussion. Thanks for your inputs it has helped the local discussion we have been having

          • Hello MD, do you think it could be useful to differentiate for patients on Anti-CD20 between the number of doses received in the ongoing discussions?
            For example, we may have several cases: the case a patient needs to begin the treatment with Anti-CD20: when to begin or postpone? Then the Debbie’s case, third (or later doses?). What to do?
            People that are due their second dose (the first full dose) in the next days/weeks should they delay the drug or the vaccine? Those people could get the vaccine before with possibly more chances of developing a better response than after later doses of the drug. Should those people be higher in priority with respect to the rest of the MS population since they could develop better response? Thank you for keeping us informed!

          • Debbie’s case has made me think what I would want to do or could be forced into doing and it is a shame that the scenario has been thrust upon us without time to think how best to react and what to advise. However, the latter issue is simple, it is not my position to advise. This needs to come for the neuros. This is their responsibility and ideally it can come from the neuros in the ABN. At the moment I suspect we dont have one common voice. I can suggest this or that, but that may change tommorrow depending on what I learn today.

            In terms of the number of doses there may be subtle differences for example it seems that 3 and 4 doses have different repopulation characteristics but I dont think the advice would need to be that different in my mind. However for someone starting it may be different. However what I first need to understand is how the vaccine is going to be dispensed. Is it simply at 12 week intervals or can some common sense be applied. As a young whipper snapper I may have one view and that of an old fart may be differnt. As someone with the prognostic features to have a rough/deadly time from COVID-19, I want to be vaccinated as soon as possible….will I get it?……I am going to be down the list.

          • I’ve been posting about my situation as can’t be the only one facing this decision with no time to fully consider and take advice. My hope is that this issue will be discussed and advice issued to help guide us.
            What I have learnt is that there can be adaptations to the dosing schedule of the vaccine on clinical reasons. We still need a steer though on when is best to take both doses between infusions. Obviously I understand that it is a balance between taking it when it’s offered to get some protection ASAP against delaying for the optimum timing and the pandemic has passed us by.
            Decision made for me last week at this present time and off for my ocrelizumab today.

    • Hi Debbie, I was told to go ahead with my Ocrevus in Feb and to wait at least 6 weeks after infusion for vaccine.

      • I wasn’t given much guidance except the 6 week gap either side of an infusion. It just happened that I was offered both the same week. My preference would be to have the vaccine leading up to an infusion in the hope of getting the best response. However, I don’t want to miss getting protected over the worst period plus now with the potential 12 week 2nd vaccine I might need to have the first jab sooner rather than later

        • Oh dear, it all comes at once!
          No idea when my GP will offer it, can’t imagine it will be that soon but apart from Ocrevus I am not any increased Covid risk. Hope your infusion went well and good luck with your vaccine. It will be a relief to have it.

          • Thanks Hannah, I was only offered it as considered CEV due to the ocrelizumab and am NHS staff albeit working from home since March. I knew it’d all come at once. Apparently I can rebook my vaccination direct soon so I’ll do that once I know when to plan around the 2 doses and my next infusion. Good luck with yours in February too

  • Ocrevous
    Corona Jab
    which will prob happen at around same time

    will neuros be getting in touch with patients about this?
    And if it’s GP’s contacting people about Corona Jab, would they know about the dosing schedule for Ocrevous and it’s need for considerable time between them one wonders? (which has just got much longer since they are looking at 12 weeks between the Corona and it’s booster.

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