SummaryBackgroundThe announcement of efficacious vaccine candidates against SARS-CoV-2 has been met with worldwide acclaim and relief. Many countries already have detailed plans for vaccine targeting based on minimising severe illness, death and healthcare burdens. Normally, relatively simple relationships between epidemiological parameters, vaccine efficacy and vaccine uptake predict the success of any immunisation programme. However, the dynamics of vaccination against SARS-CoV-2 is made more complex by age-dependent factors, changing levels of infection and the potential relaxation of non-pharmaceutical interventions (NPIs) as the perceived risk declines.MethodsIn this study we use an age-structured mathematical model, matched to a range of epidemiological data in the UK, that also captures the roll-out of a two-dose vaccination programme targeted at specific age groups.FindingsWe consider the interaction between the UK vaccination programme and future relaxation (or removal) of NPIs. Our predictions highlight the population-level risks of early relaxation leading to a pronounced wave of infection, hospital admissions and deaths. Only vaccines that offer high infection-blocking efficacy with high uptake in the general population allow relaxation of NPIs without a huge surge in deaths.InterpretationWhile the novel vaccines against SARS-CoV-2 offer a potential exit strategy for this outbreak, this is highly contingent on the infection-blocking (or transmission-blocking) action of the vaccine and the population uptake, both of which need to be carefully monitored as vaccine programmes are rolled out in the UK and other countries.Research in contextEvidence before this studyVaccination has been seen as a key tool in the fight against SARS-CoV-2. The vaccines already developed represent a major technological achievement and have been shown to generate significant immune responses, as well as offering considerable protection against disease. However, to date there is limited information on the degree of infection-blocking these vaccines are likely to induce. Mathematical models have already successfully been used to consider age- and risk-structured targeting of vaccination, highlighting the importance of prioritising older and high-risk individuals.Added value of this studyTranslating current knowledge and uncertainty of vaccine behaviour into meaningful public health messages requires models that fully capture the within-country epidemiology as well as the complex roll-out of a two-dose vaccination programme. We show that under reasonable assumptions for vaccine efficacy and uptake the UK is unlikely to reach herd immunity, which means that non-pharmaceutical interventions cannot be released without generating substantial waves of infection.Implications of all the available evidenceVaccination is likely to provide substantial individual protection to those receiving two doses, but the degree of protection to the wider population is still uncertain. While substantial immunisation of the most vulnerable groups will allow for some relaxation of controls, this must be done gradually to prevent large scale public health consequences.