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:
- 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.
- 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.
- 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:
- 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.
- 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.
- 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.
- 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.
The British Society for Immunology is committed to playing our part and working with Government, our members and the public to ensure that COVID-19 vaccine rollout has the maximum impact in saving lives. We continue to liaise with the Chief Medical Officer and the Department for Health and Social Care on these issues and stand ready to assist whenever needed. We will also continue to support and work through our membership to do all we can to defeat this virus and to steer us all through this pandemic.
- 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
- Sahin et al. 2020 BNT162b2 induces SARS-CoV-2-neutralising antibodies and T cells in humans. medRxiv, doi: 10.1101/2020.12.09.20245175
- FDA briefing document. 10 December 2020. Pfizer-BioNTech COVID-19 Vaccine. https://www.fda.gov/media/144245/download
- 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
- 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
- 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
- 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
For any queries, please contact BSI Head of External Affairs, Jennie Evans.
Statement released: 4 January 2021