Modelling optimal vaccination strategy for SARS-CoV-2 in the UK

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Abstract

The COVID-19 outbreak has highlighted our vulnerability to novel infections.

Faced with this threat and no effective treatment, in line with many other countries, the UK adopted enforced social distancing (lockdown) to reduce transmission—successfully reducing the reproductive number R below one. However, given the large pool of susceptible individuals that remain, complete relaxation of controls is likely to generate a substantial further outbreak. Vaccination remains the only foreseeable means of both containing the infection and returning to normal interactions and behaviour. Here, we consider the optimal targeting of vaccination within the UK, with the aim of minimising future deaths or quality adjusted life year (QALY) losses. We show that, for a range of assumptions on the action and efficacy of the vaccine, targeting older age groups first is optimal and may be sufficient to stem the epidemic if the vaccine prevents transmission as well as disease.

Author summary

In line with most other countries across the globe, and in the absence of a vaccine or pharmaceutical treatments, the UK has relied heavily upon non-pharmaceutical social measures to control the impact of the COVID-19 pandemic. While this has proved effective in reducing the healthcare burden compared to an uncontrolled outbreak, this is achieved to the detriment of the economy, education and many other societal factors. As vaccines are developed which mitigate the disease, it is of great importance that they are delivered in an optimal manner—reducing mortality and healthcare demands. Using an age-structured mathematical model of SARS-CoV-2 transmission, we test different vaccine ordering strategies to identify which members of society should be targeted for vaccination first in order to achieve a specified health objective. In all scenarios we find vaccinating the most elderly and vulnerable first to have the greatest impact, though the ultimate success of any vaccination scheme will be highly contingent on the characteristics of the vaccine itself and the level of population uptake.

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Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P Polack, Stephen J. Thomas, Nicholas R.E. Kitchin … (2023)

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

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Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Lindsey Baden, Hana El Sahly, Brandon Essink … (2020)

Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)

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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

Merryn Voysey, Sue Ann Costa Clemens, Shabir Madhi … (2022)

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; p interaction =0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. Funding UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

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Author and article information

Contributors

Sam Moore:

ORCID: https://orcid.org/0000-0001-7786-5342

Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing

Edward M. Hill:

ORCID: https://orcid.org/0000-0002-2992-2004

Role: Data curationRole: SoftwareRole: ValidationRole: Writing – review & editing

Louise Dyson:

ORCID: https://orcid.org/0000-0001-9788-4858

Role: SoftwareRole: ValidationRole: Writing – review & editing

Michael J. Tildesley:

ORCID: https://orcid.org/0000-0002-6875-7232

Role: ConceptualizationRole: SoftwareRole: ValidationRole: Writing – review & editing

Matt J. Keeling:

ORCID: https://orcid.org/0000-0003-4639-4765

Role: ConceptualizationRole: Data curationRole: MethodologyRole: SoftwareRole: ValidationRole: Writing – review & editing

Alex Perkins: Role: Editor

Journal

Journal ID (nlm-ta): PLoS Comput Biol

Journal ID (iso-abbrev): PLoS Comput Biol

Journal ID (publisher-id): plos

Journal ID (pmc): ploscomp

Title: PLoS Computational Biology

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Print): 1553-734X

ISSN (Electronic): 1553-7358

Publication date Collection: May 2021

Publication date (Electronic): 6 May 2021

Volume: 17

Issue: 5

Electronic Location Identifier: e1008849

Affiliations

[001] The Zeeman Institute for Systems Biology & Infectious Disease Epidemiology Research, School of Life Sciences and Mathematics Institute, University of Warwick, Coventry, United Kingdom

University of Notre Dame, UNITED STATES

Author notes

The authors have declared that no competing interests exist.

* E-mail: Samuel.E.Moore@ 123456warwick.ac.uk (SM); M.J.Keeling@ 123456warwick.ac.uk (MJK)

Author information

Sam Moore https://orcid.org/0000-0001-7786-5342

Edward M. Hill https://orcid.org/0000-0002-2992-2004

Louise Dyson https://orcid.org/0000-0001-9788-4858

Michael J. Tildesley https://orcid.org/0000-0002-6875-7232

Matt J. Keeling https://orcid.org/0000-0003-4639-4765

Article

Publisher ID: PCOMPBIOL-D-20-01845

DOI: 10.1371/journal.pcbi.1008849

PMC ID: 8101958

PubMed ID: 33956791

SO-VID: 12cdce71-6b6b-40b4-a083-b9cc4a29e282

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 9 October 2020

Date accepted : 3 March 2021

Page count

Figures: 9, Tables: 1, Pages: 20

Funding

Funded by: National Institute for Health Research

Award ID: NIHR200411

Funded by: funder-id http://dx.doi.org/10.13039/501100000266, Engineering and Physical Sciences Research Council;

Award ID: EP/S022244/1

Funded by: Medical Research Council

Award ID: MR/V009761/1

This report is independent research funded by the National Institute for Health Research (NIHR, https://www.nihr.ac.uk/) [Policy Research Programme, Mathematical Economic Modelling for Vaccination and Immunisation Evaluation, and Emergency Response; NIHR200411]. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. It has also been supported by the Engineering and Physical Sciences Research Council ( https://epsrc.ukri.org/) through the MathSys CD [grant number EP/S022244/1] and by the Medical Research Council through the COVID-19 Rapid Response Rolling Call [grant number MR/V009761/1]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Data Availability Data on cases were obtained from the COVID-19 Hospitalisation in England Surveillance System (CHESS) data set that collects detailed data on patients infected with COVID-19. Data on COVID-19 deaths were obtained from Public Health England. These data contain confidential information, with public data deposition non-permissible for socioeconomic reasons. The CHESS data resides with the National Health Service ( ww.nhs.gov.uk) whilst the death data are available from Public Health England ( www.phe.gov.uk). Interested readers wanting similar data may wish to contact coronavirus-tracker@ 123456phe.gov.uk .

Outbreaks COVID-19

ScienceOpen disciplines: Quantitative & Systems biology

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ScienceOpen disciplines: Quantitative & Systems biology

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Modelling optimal vaccination strategy for SARS-CoV-2 in the UK

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Most cited references 51

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

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

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