Given the current epidemiology of covid-19 in the UK, the public health imperative is to vaccinate as many of the most vulnerable people as fast as possible.  In response, the Joint Committee on Vaccination and Immunisation (JCVI) advised on 30 December 2020 that the interval between the two doses of both vaccines could be extended to 12 weeks, with prioritisation of delivery of the first dose. [2, 3] Every second dose of the vaccine delivered is one less dose to give to someone who has no protection. Based on the mortality in those over 80 years of age during the first wave, and assuming an efficacy from the first dose of 70-90% (described below), it is estimated that one death could be prevented for every 260-330 first doses of the vaccine given. One million additional first dose vaccines may therefore prevent around 3000-4000 deaths in this age group. The first nine priority groups identified for vaccination should target 99% of potentially preventable deaths from covid-19 .
There has been understandable concern about the change in schedule among healthcare professionals and the public. Patients who were told they would receive a second dose of the Pfizer vaccine in three weeks are now being asked to rebook those appointments. From a public health perspective, however, this is a necessary step that will save lives. The World Health Organization’s Strategic Advisory Group of Experts (different to the UK government’s SAGE advisory committee) has also made provision for countries to delay the second dose for a few weeks to maximise the number of individuals benefiting from a first dose. 
Three covid-19 vaccines have now been approved for use in the UK; – Pfizer-BioNTech messenger RNA (mRNA) vaccine the Oxford/AstraZeneca (AZ) adenovirus-vector vaccine, and the Moderna RNA vaccine. [5,6] The vaccines encode for the SARS-CoV2 spike protein to provide an intracellular antigen and induce a host immune response. [7,8]
The Pfizer-BioNTech and Oxford/AstraZeneca vaccines vaccines are reported to offer high protection after two doses. For the Oxford/AZ vaccine, a half first dose and a standard second dose was initially reported to provide higher protection, but subsequent analyses suggest that this may be explained by a longer time interval between doses.  The immune response takes two to three weeks to develop after the first vaccine dose. An exploratory analysis by Oxford/AstraZeneca indicates that from 22 days after the first standard dose, vaccine efficacy (VE) is 73%, with protective immunity likely to last at least 12 weeks from the first dose. 
For the Pfizer vaccine, the published trial reported vaccine efficacy of 52% after the first dose (39 cases in the vaccine group and 82 cases in the placebo group (95% CI, 29.5 to 68.4)) including cases occurring from day 1 until the second dose.  In further analyses, Public Health England (PHE) calculated an efficacy of 89% after the first dose, based on cases observed from day 15 (and up to day 21). PHE’s figure is higher because it excludes cases of laboratory confirmed covid-19 that occurred too soon after the first dose to be true vaccine failures. [3, 5, 7] For a similar mRNA vaccine developed by Moderna, efficacy from 15 days after the first dose was an estimated 92% after a median follow-up of 28 days (range: 1 to 108 days). 
As the final method of production of the spike protein is common to all these vaccines, there is no immunological reason to expect the immune response to a single dose of the Pfizer vaccine to be less robust or to fall away more rapidly than the response to a single dose of the AZ vaccine.
Despite reports by the New York Times, JCVI currently advises that individuals should complete the schedule with a second dose of the same covid-19 vaccine, up to 12 weeks later.  The Green Book (information on vaccines and vaccination procedures published by PHE) also advises that every effort should be made to complete the course with the same vaccine. If the same vaccine is not available, or if the initial vaccine is unknown, it is reasonable to offer the locally available product as a second dose to complete the schedule. In JCVI’s view it is better in these exceptional circumstances to have a second dose of an alternative vaccine, than to have no second dose at all. This option is preferred if the individual is likely to be at immediate high risk or is considered unlikely to attend again. Mixed schedules of vaccines using broadly the same antigen are commonly recommended to encourage high coverage, such as with HPV vaccines. Studies are ongoing to determine whether immune responses to mixed vaccine schedules are acceptable.
Current vaccines can prevent symptomatic infections and hospitalisations, but we do not yet know whether they prevent asymptomatic infection and transmission. Until we do, the correct strategy is to focus on preventing disease. Surveillance of the long-term safety and effectiveness of covid-19 vaccines is being conducted through the MHRA and PHE, including studies to determine whether vaccination prevents transmission. If it does, the focus of the second phase of the vaccine strategy could shift from preventing disease to preventing transmission. Once vulnerable groups are protected, phase two of the programme may therefore target those populations most likely to be fuelling transmission. Evidence from disease surveillance and sero-epidemiological studies in all age groups will be reviewed by JCVI to improve our understanding of which groups are driving transmission in the UK.
JCVI will continue to advise in a timely manner on the optimal vaccine strategy, paying careful attention to the evolving epidemiology. JCVI will closely monitor post authorisation surveillance by the MHRA and PHE to assess the long term safety of the vaccines. We will receive regular reports on coverage and play our part in monitoring the programme as a whole. The massive logistical exercise of getting the supplies to the vaccinators and ensuring there is sufficient capacity to administer the vaccines to as many people as possible in the shortest period of time is the role of the NHS. We do not underestimate the challenges ahead.
At this point in the pandemic, we must do all we can to provide protection across all vulnerable populations as quickly as possible. Vaccine supply and NHS capacity are key factors in delivery of the programme and prioritising the first dose is a pragmatic and scientifically justifiable approach, which will result in more widespread protection in vulnerable groups. Ultimately, prioritising the first dose will save more lives.
Anthony Harnden, Deputy Chair, Joint Committee on Vaccination and Immunisation and Professor of Primary Care at University of Oxford.
Andrew Earnshaw, Head of the Joint Committee on Vaccination and Immunisation Scientific Secretariat.
Mary Ramsay, Head of Immunisation, Public Health England.
Competing interests: AH is a university of Oxford employee, but was not involved in the clinical trials of the Oxford vaccine. AE and MR none declared.
Wei Shen Lim, Chair of the Joint Committee on Vaccination and Immunisation Committee (COVID-19), provided comments on an early draft.
 Public Health England – Investigation of novel SARS-COV-2 variant. Variant of Concern 2020/12/01 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/947048/Technical_Briefing_VOC_SH_NJL2_SH2.pdf
 Joint Committee on Vaccination and Immunisation: advice on priority groups for COVID-19 vaccination, 30 December 2020. https://www.gov.uk/government/publications/priority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020/joint-committee-on-vaccination-and-immunisation-advice-on-priority-groups-for-covid-19-vaccination-30-december-2020
 Optimising the COVID-19 vaccination programme for maximum short-term impact. Short statement from the Joint Committee on Vaccination and Immunisation (JCVI). 31 December 2020
 COVID-19 Virtual Press conference transcript – 5 January 2021 (who.int)
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 Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, et al. 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. Lancet. 2020 Dec 8:S0140-6736(20)32661-1. doi: 10.1016/S0140-6736(20)32661-1.
 Emergency Use Authorization for Pfizer-BioNTech COVID-19 Vaccine Review Memo (fda.gov)
 Vaccines and Related Biological Products Advisory Committee December 17, 2020 Meeting Briefing Document – FDA
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