Optimising Vaccine Dose in Inoculation against SARS-CoV-2, a Multi-Factor Optimisation Modelling Study to Maximise Vaccine Safety and Efficacy
Developing a vaccine against the global pandemic SARS-CoV-2 is a critical area of active research. Modelling can be used to identify optimal vaccine dosing; maximising vaccine efficacy and safety and minimising cost. We calibrated statistical models to published dose-dependent seroconversion and adv...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/2/78 |
| _version_ | 1797408255509528576 |
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| author | John Benest Sophie Rhodes Matthew Quaife Thomas G. Evans Richard G. White |
| author_facet | John Benest Sophie Rhodes Matthew Quaife Thomas G. Evans Richard G. White |
| author_sort | John Benest |
| collection | DOAJ |
| description | Developing a vaccine against the global pandemic SARS-CoV-2 is a critical area of active research. Modelling can be used to identify optimal vaccine dosing; maximising vaccine efficacy and safety and minimising cost. We calibrated statistical models to published dose-dependent seroconversion and adverse event data of a recombinant adenovirus type-5 (Ad5) SARS-CoV-2 vaccine given at doses 5.0 × 10<sup>10</sup>, 1.0 × 10<sup>11</sup> and 1.5 × 10<sup>11</sup> viral particles. We estimated the optimal dose for three objectives, finding: (A) the minimum dose that may induce herd immunity, (B) the dose that maximises immunogenicity and safety and (C) the dose that maximises immunogenicity and safety whilst minimising cost. Results suggest optimal dose [95% confidence interval] in viral particles per person was (A) 1.3 × 10<sup>11</sup> [0.8–7.9 × 10<sup>11</sup>], (B) 1.5 × 10<sup>11</sup> [0.3–5.0 × 10<sup>11</sup>] and (C) 1.1 × 10<sup>11</sup> [0.2–1.5 × 10<sup>11</sup>]. Optimal dose exceeded 5.0 × 10<sup>10</sup> viral particles only if the cost of delivery exceeded £0.65 or cost per 10<sup>11</sup> viral particles was less than £6.23. Optimal dose may differ depending on the objectives of developers and policy-makers, but further research is required to improve the accuracy of optimal-dose estimates. |
| first_indexed | 2024-03-09T03:55:46Z |
| format | Article |
| id | doaj.art-9d6433ec16164c10b3a94f035e96db67 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T03:55:46Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-9d6433ec16164c10b3a94f035e96db672023-12-03T14:21:32ZengMDPI AGVaccines2076-393X2021-01-01927810.3390/vaccines9020078Optimising Vaccine Dose in Inoculation against SARS-CoV-2, a Multi-Factor Optimisation Modelling Study to Maximise Vaccine Safety and EfficacyJohn Benest0Sophie Rhodes1Matthew Quaife2Thomas G. Evans3Richard G. White4Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UKDepartment of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UKDepartment of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UKVaccitech Ltd., The Schrodinger Building, Heatley Road, The Oxford Science Park, Oxford OX4 4GE, UKDepartment of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UKDeveloping a vaccine against the global pandemic SARS-CoV-2 is a critical area of active research. Modelling can be used to identify optimal vaccine dosing; maximising vaccine efficacy and safety and minimising cost. We calibrated statistical models to published dose-dependent seroconversion and adverse event data of a recombinant adenovirus type-5 (Ad5) SARS-CoV-2 vaccine given at doses 5.0 × 10<sup>10</sup>, 1.0 × 10<sup>11</sup> and 1.5 × 10<sup>11</sup> viral particles. We estimated the optimal dose for three objectives, finding: (A) the minimum dose that may induce herd immunity, (B) the dose that maximises immunogenicity and safety and (C) the dose that maximises immunogenicity and safety whilst minimising cost. Results suggest optimal dose [95% confidence interval] in viral particles per person was (A) 1.3 × 10<sup>11</sup> [0.8–7.9 × 10<sup>11</sup>], (B) 1.5 × 10<sup>11</sup> [0.3–5.0 × 10<sup>11</sup>] and (C) 1.1 × 10<sup>11</sup> [0.2–1.5 × 10<sup>11</sup>]. Optimal dose exceeded 5.0 × 10<sup>10</sup> viral particles only if the cost of delivery exceeded £0.65 or cost per 10<sup>11</sup> viral particles was less than £6.23. Optimal dose may differ depending on the objectives of developers and policy-makers, but further research is required to improve the accuracy of optimal-dose estimates.https://www.mdpi.com/2076-393X/9/2/78dosingdose-responseadenovirus-vectored vaccinesdose dynamicsCOVID-19 |
| spellingShingle | John Benest Sophie Rhodes Matthew Quaife Thomas G. Evans Richard G. White Optimising Vaccine Dose in Inoculation against SARS-CoV-2, a Multi-Factor Optimisation Modelling Study to Maximise Vaccine Safety and Efficacy Vaccines dosing dose-response adenovirus-vectored vaccines dose dynamics COVID-19 |
| title | Optimising Vaccine Dose in Inoculation against SARS-CoV-2, a Multi-Factor Optimisation Modelling Study to Maximise Vaccine Safety and Efficacy |
| title_full | Optimising Vaccine Dose in Inoculation against SARS-CoV-2, a Multi-Factor Optimisation Modelling Study to Maximise Vaccine Safety and Efficacy |
| title_fullStr | Optimising Vaccine Dose in Inoculation against SARS-CoV-2, a Multi-Factor Optimisation Modelling Study to Maximise Vaccine Safety and Efficacy |
| title_full_unstemmed | Optimising Vaccine Dose in Inoculation against SARS-CoV-2, a Multi-Factor Optimisation Modelling Study to Maximise Vaccine Safety and Efficacy |
| title_short | Optimising Vaccine Dose in Inoculation against SARS-CoV-2, a Multi-Factor Optimisation Modelling Study to Maximise Vaccine Safety and Efficacy |
| title_sort | optimising vaccine dose in inoculation against sars cov 2 a multi factor optimisation modelling study to maximise vaccine safety and efficacy |
| topic | dosing dose-response adenovirus-vectored vaccines dose dynamics COVID-19 |
| url | https://www.mdpi.com/2076-393X/9/2/78 |
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