WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Laboratory of Data Discovery for Health Limited, Hong Kong Science and Technology Park, New Territories, Hong Kong, China.
BMC Med. 2022 Oct 25;20(1):409. doi: 10.1186/s12916-022-02600-0.
Dose fractionation of a coronavirus disease 2019 (COVID-19) vaccine could effectively accelerate global vaccine coverage, while supporting evidence of efficacy, immunogenicity, and safety are unavailable, especially with emerging variants.
We systematically reviewed clinical trials that reported dose-finding results and estimated the dose-response relationship of neutralizing antibodies (nAbs) of COVID-19 vaccines using a generalized additive model. We predicted the vaccine efficacy against both ancestral and variants, using previously reported correlates of protection and cross-reactivity. We also reviewed and compared seroconversion to nAbs, T cell responses, and safety profiles between fractional and standard dose groups.
We found that dose fractionation of mRNA and protein subunit vaccines could induce SARS-CoV-2-specific nAbs and T cells that confer a reasonable level of protection (i.e., vaccine efficacy > 50%) against ancestral strains and variants up to Omicron. Safety profiles of fractional doses were non-inferior to the standard dose.
Dose fractionation of mRNA and protein subunit vaccines may be safe and effective, which would also vary depending on the characteristics of emerging variants and updated vaccine formulations.
将新型冠状病毒病 2019（COVID-19）疫苗进行剂量分割可有效加快全球疫苗接种覆盖率，尽管目前尚无关于疗效、免疫原性和安全性的支持证据，尤其是在出现新变种的情况下。
我们系统地综述了报告剂量探索结果的临床试验，并使用广义加性模型估算了 COVID-19 疫苗的中和抗体（nAb）的剂量反应关系。我们使用之前报告的保护相关性和交叉反应性，预测了疫苗对原始株和变体的疗效。我们还综述并比较了 fractional 和 standard 剂量组之间的 nAb、T 细胞反应和安全性特征的血清转化率。
我们发现，mRNA 和蛋白亚单位疫苗的剂量分割可诱导 SARS-CoV-2 特异性 nAb 和 T 细胞，从而为针对原始株和变异株（包括奥密克戎株）提供合理水平的保护（即疫苗效力>50%）。 fractional 剂量的安全性与标准剂量相当。
mRNA 和蛋白亚单位疫苗的剂量分割可能是安全有效的，这也将取决于新出现的变异株的特征和更新的疫苗配方。
