Vaccination has had a huge impact on the pandemic in the UK. The initial roll-out of vaccine began in December of 2020 and has dramatically reduced the number of cases while having an even larger effect on hospital admissions and deaths. Modelling and analysis from the Zeeman Institute has been key in underpinning JCVI decisions on vaccination, from early priority ordering to the deployment of booster doses, and in understanding how vaccines and non-pharmaceutical interventions interact.

Our publications and pre-prints on vaccination against COVID are:

Matt J. Keeling, Edward M Hill, Stavros Petrou, Phuong Bich Tran, May Ed Png, Sophie Staniszewska, Corinna Clark, Katie Hassel, Julia Stowe, Nick Andrews (2024) Cost-effectiveness of routine COVID-19 adult vaccination programmes in England. medRXiv Pre-Print

In England, and many other countries, immunity to SARS-CoV-2 infection is highly heterogeneous. Immunity has been acquired through natural infection and vaccination, while protection has been lost through waning immunity and viral mutation. During the height of the pandemic in England, the main aim was to rapidly protect the population and large supplies of vaccine were pre-purchased, eliminating the need for cost-effective calculations. As we move to an era where for the majority of the population SARS-CoV-2 infections cause relatively mild disease, and vaccine stocks need to be re-purchased, it is important we consider the cost-effectiveness and economic value of COVID-19 vaccination programmes. The historic offer of COVID-19 vaccination to those 65 and over for the autumn 2023 programme and those over 75 for the spring 2023 programme, aligns with our cost-effective threshold for pre-purchased vaccine when the only cost was administration. However, for future programmes, when vaccine costs are included, the age-thresholds slowly increase thereby demonstrating the continued importance of protecting the eldest and most vulnerable in the population. We find that at a total cost of £30 (for vaccine and administration) universal vaccination is only cost-effective for those over 75; while at £60 universal vaccination is only cost-effective for those over 80.

JCVI statement on COVID-19 vaccination in 2025.

Ioana Bouros, Edward M. Hill, Matt J. Keeling, Sam Moore , Robin N. Thompson (2024) TPrioritising older individuals for COVID-19 booster vaccination leads to optimal public health outcomes in a range of socio-economic settings. PLoS Comp. Biol. 20, e1012309. https://doi.org/10.1371/journal.pcbi.1012309

Computational modelling is used increasingly to assess interventions against infectious diseases. For COVID-19, booster vaccines are being deployed worldwide to mitigate the effect of waning immunity following past infections and vaccinations, and to protect against new SARS-CoV-2 variants. However, booster vaccine availability is limited, making it necessary to consider who should receive booster vaccinations. It is essential that booster vaccine prioritisation is considered not only in the context of high income countries, but also low and middle income countries where the population age structure is very different. We have therefore developed a computational model to guide booster vaccination prioritisation in different socio-economic settings. We show that vaccinated populations can have different compositions between countries, even when identical booster vaccination strategies are adopted. Despite these differences, our modelling results suggest that booster vaccination strategies prioritising the oldest individuals lead to the best possible public health outcomes, due to the substantial skew in the risk of severe outcomes of infection towards older (and other vulnerable) hosts. This remains true even when quantifying the extent of premature, rather than absolute, mortality. This research therefore supports policy advice recommending prioritisation of older individuals for booster vaccines in countries worldwide when vaccine supply is limited.

Matt J. Keeling, Samuel Moore, Bridget S. Penman & Edward M Hill (2023) The impacts of SARS-CoV-2 vaccine dose separation and targeting on the COVID-19 epidemic in England. Nature Comms 14, 740. https://doi.org/10.1038/s41467-023-35943-0

In late 2020, the JCVI (the Joint Committee on Vaccination and Immunisation, which provides advice to the Department of Health and Social Care, England) made two important recommendations for the initial roll-out of the COVID-19 vaccine. The first was that vaccines should be targeted to older and vulnerable people, with the aim of maximally preventing disease rather than infection. The second was to increase the interval between first and second doses from 3 to 12 weeks.

In this paper, we re-examined these recommendations through a mathematical model of SARS-CoV-2 infection in England. We show that targeting the most vulnerable had the biggest immediate impact (compared to targeting younger individuals who may be more responsible for transmission). The 12-week delay was also highly beneficial, estimated to have averted between 32-72 thousand hospital admissions and 4-9 thousand deaths over the first ten months of the campaign (December 2020–September 2021) depending on the assumed interaction between dose interval and efficacy.

Sam Moore, Edward M. Hill, Louise Dyson, Michael J. Tildesley, Matt J. Keeling (2022) Retrospectively modeling the effects of increased global vaccine sharing on the COVID-19 pandemic Nature Medicine 28, 2416–2423. https://doi.org/10.1038/s41591-022-02064-y

We use an age-structured model of SARS-CoV-2 dynamics, matched to national data from 152 countries, to investigate the global impact of different vaccine sharing protocols during 2021. We assume a direct relationship between the emergence of variants with increased transmissibility and the cumulative amount of global infection, such that lower global prevalence leads to a lower reproductive number within each country. We compare five vaccine sharing scenarios, from the current situation, through sharing once a particular within-country threshold is reached (e.g. all over 40s have received 2 doses), to full sharing where all countries achieve equal age-dependent vaccine deployment.

Compared to the observed distribution of vaccine uptake, we estimate full vaccine sharing would have generated a 1.5% (PI -0.1 - 4.5%) reduction in infections and a 11.3% (PI 0.6 - 23.2%) reduction in mortality globally by January 2022. The greatest benefit of vaccine sharing would have been experienced by low and middle income countries, who see an average 5.2% (PI 2.5% - 10.4%) infection reduction and 26.8% (PI 24.1% - 31.3%) mortality reduction. Many high income countries, that have had high vaccine uptake (most notably Canada, Chile, UK and USA), suffer increased infections and mortality under most of the sharing protocols investigated, assuming no other counter measures had been taken. However, if reductions in vaccine supply in these countries had been offset by prolonged use of non-pharmaceutical intervention measures, we predict far greater reductions in global infection and mortality of 64.5% (PI 62.6% - 65.4%) and 62.8% (PI 44.0% - 76.3%), respectively.

 

Keeling, M.J., Moore, S. (2022) "An assessment of the vaccination of school-aged children in England" BMC Medicine 20: 196. https://doi.org/10.1186/s12916-022-02379-0

Vaccination, initially targeting the elderly and vulnerable but later expanded to the entire adult population, has been transformative in the control of SARS-CoV-2 in England. However, early concerns over adverse events and the lower risk associated with infection in younger individuals means that the expansion of the vaccine programme to those under 18 year of age needs to be rigorously and quantitatively assessed. In this paper we use a bespoke mathematical model matched to case and hospital data for England to calculate the potential impact of vaccinating 12-17 and 5-11 year olds. Projections generated in June 2021 suggested that an expansion of the vaccine programme to those 12-17 years old could generate substantial reductions in infection, hospital admission and deaths in the entire population, depending on population behaviour following the relaxation of control measures. The benefits within the 12-17 year old cohort were less marked, saving between 656 and 1077 (95% prediction interval 281-2260) hospital admissions and between 22 and 38 (95% PI 9-91) deaths depending on assumed population behaviour. For the more recent model formulation (November 2021), the benefits within this age group are reduced, saving on average 631 (95% PI 304-1286) hospital admissions and 11 (95% PI 5-28) deaths for 80% vaccine uptake, while the benefits to the wider population represent a reduction of 8-10% in hospital admissions and deaths. The vaccination of 5-11 year olds is projected to have a far smaller impact, in part due to the later roll-out of vaccines to this age-group.

 

Keeling, M.J., Thomas, A., Hill, E.M., Thompson, R.N., Dyson, L., Tildesley, M.J., Moore, S. (2021) "Waning, Boosting and a Path to Endemicity for SARS-CoV-2" medRxiv. https://doi.org/10.1101/2021.11.05.21265977

In many countries, an extensive vaccination programme has substantially reduced the public-health impact of SARS-CoV-2, limiting the number of hospital admissions and deaths compared to an unmitigated epidemic. The observed waning of vaccine efficacy over time suggests that booster doses may be required to maintain population immunity especially in the most vulnerable groups. Here, using data and models for England, we consider the dynamics of COVID-19 over a two-year time-frame, and the role that booster vaccinations can play in mitigating the worst effects. Although formulated for the Delta variant, this paper has key implications for Omicron.

 

Hill, E.M., Keeling, M.J. (2021) "Comparison between one and two dose SARS-CoV-2 vaccine prioritization for a fixed number of vaccine doses" Interface. 18(182): 20210214. https://doi.org/10.1098/rsif.2021.0214

Focusing on data from England, we investigated prioritisation of a one dose or two dose SARS-CoV-2 vaccination schedule given a fixed number of vaccine doses and with respect to a measure of maximising averted deaths. This work highlighted the advantage of a longer separation between first and second, as it enables more vulnerable people to be protected early in the epidemic, and therefore reduces hospital admissions and deaths from the pandemic.

Gog JR, Hill EM, Danon L, Thompson RN. (2021) Vaccine escape in a heterogeneous population: insights for SARS-CoV-2 from a simple model Roy. Soc. Open Sci., 8:210530. DOI: 10.1098/rsos.210530

By developing and analysing a mathematical model of two population groupings with differing vulnerability and contact rates, this paper explores the impact of the deployment of vaccines among the population on the reproduction ratio, cases, disease abundance and vaccine escape pressure. The results from this model illustrate two insights: (i) vaccination aimed at reducing prevalence could be more effective at reducing disease than directly vaccinating the vulnerable; (ii) the highest risk for vaccine escape can occur at intermediate levels of vaccination. This work demonstrates a key principle: the careful targeting of vaccines towards particular population groups could reduce disease as much as possible while limiting the risk of vaccine escape.

Moore, S., Hill, E.M., Tildesley, M., Dyson, L., Keeling, M.J. (2021) "Vaccination and non-pharmaceutical interventions for COVID-19: a mathematical modelling study " Lancet Infectious Diseases. 21(6): 793-802. https://doi.org/10.1016/S1473-3099(21)00143-2

By combining models of vaccination with the methods of forwards projection, we considered the interaction between the relaxation of non-pharamaceutical interventions (NPIs) and the protection offered by the vaccine.

This paper set the tone for unlocking the UK in 2021: Our modelled scenarios highlighted the risks associated with early or rapid relaxation of NPIs, stressing the need for slow release of control measures if large-scale waves of infection are to be avoided.

We conclude that while the vaccines against SARS-CoV-2 offer a potential exit strategy for the pandemic, success is highly contingent on the precise vaccine properties and population uptake.

 

Moore, S., Hill, E.M., Dyson, L., Tildesley, M., Keeling, M.J. (2021) "Modelling optimal vaccination strategy for SARS-CoV-2 in the UKLink opens in a new window" PLoS Comp. Biol. 17(5): e1008849. https://doi.org/10.1371/journal.pcbi.1008849

In an early extension to the Warwick COVID model, we introduced a vaccinated class and a population with health conditions that are believed to have a significant impact on COVID-19 outcomes. At the time a number of different vaccine candidates were in development and the results from clinical trials were not fully available, leading to a large degree of uncertainty regarding the performance of these products. We therefore tested a range of efficacies (including reduced efficacy in the elderly) and three different types of vaccine each delivering a different level of protection.

This paper highlighted the importance of prioritising vaccination towards the oldest and most vulnerable in the population, as this generates the maximum reduction in deaths and other severe outcomes.

Figure: Impact of vaccination targeted at different age-groups. Orange: targeting by age, the optimal is to vaccinate the oldest age groups first. Purple: including co-morbidities, these are optimally ordered between 60 and 80 year olds. Blue: random vaccination.