Benest John, Rhodes Sophie, Quaife Matthew, Evans Thomas G, White Richard G
Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Vaccitech Ltd., The Schrodinger Building, Heatley Road, The Oxford Science Park, Oxford OX4 4GE, UK.
Vaccines (Basel). 2021 Jan 22;9(2):78. doi: 10.3390/vaccines9020078.
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, 1.0 × 10 and 1.5 × 10 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 [0.8-7.9 × 10], (B) 1.5 × 10 [0.3-5.0 × 10] and (C) 1.1 × 10 [0.2-1.5 × 10]. Optimal dose exceeded 5.0 × 10 viral particles only if the cost of delivery exceeded £0.65 or cost per 10 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.
研发针对全球大流行的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的疫苗是当前积极研究的关键领域。建模可用于确定最佳疫苗剂量，以最大化疫苗效力和安全性并最小化成本。我们根据已发表的重组5型腺病毒（Ad5）SARS-CoV-2疫苗在5.0×10、1.0×10和1.5×10病毒颗粒剂量下的剂量依赖性血清转化和不良事件数据，对统计模型进行了校准。我们针对三个目标估计了最佳剂量，结果发现：（A）可能诱导群体免疫的最小剂量；（B）使免疫原性和安全性最大化的剂量；（C）使免疫原性和安全性最大化同时使成本最小化的剂量。结果表明，每人每剂病毒颗粒的最佳剂量[95%置信区间]为：（A）1.3×10[0.8 - 7.9×10]；（B）1.5×10[0.3 - 5.0×10]；（C）1.1×10[0.2 - 1.5×10]。仅当接种成本超过0.65英镑或每10个病毒颗粒的成本低于6.23英镑时，最佳剂量才会超过5.0×10病毒颗粒。最佳剂量可能因研发人员和政策制定者的目标而异，但需要进一步研究以提高最佳剂量估计的准确性。
