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 (Hong Kong).
Laboratory of Data Discovery for Health Limited (D24H), Hong Kong Science and Technology Park, Hong Kong, China (Hong Kong).
JMIR Public Health Surveill. 2024 Jul 12;10:e49812. doi: 10.2196/49812.
With the emergence of SARS-CoV-2 variants that have eluded immunity from vaccines and prior infections, vaccine shortages and vaccine effectiveness pose unprecedented challenges for governments in expanding booster vaccination programs. The fractionation of vaccine doses might be an effective strategy for helping society to face these challenges, as fractional doses may have efficacies comparable with those of the standard doses.
This study aims to investigate the relationship between vaccine immunogenicity and protection and to project efficacies of fractional doses of vaccines for COVID-19 by using neutralizing antibody levels.
In this study, we analyzed the relationship between in vitro neutralization levels and the observed efficacies against both asymptomatic infection and symptomatic infection, using data from 13 studies of 10 COVID-19 vaccines and from convalescent cohorts. We further projected efficacies for fractional doses, using neutralization as an intermediate variable, based on immunogenicity data from 51 studies included in our systematic review.
In comparisons with the convalescent level, vaccine efficacy against asymptomatic infection and symptomatic infection increased from 8.8% (95% CI 1.4%-16.1%) to 71.8% (95% CI 63%-80.7%) and from 33.6% (95% CI 23.6%-43.6%) to 98.6% (95% CI 97.6%-99.7%), respectively, as the mean neutralization level increased from 0.1 to 10 folds of the convalescent level. Additionally, mRNA vaccines provided the strongest protection, which decreased slowly for fractional dosing with dosages between 50% and 100% of the standard dose. We also observed that although vaccine efficacy increased with the mean neutralization level, the rate of this increase was slower for vaccine efficacy against asymptomatic infection than for vaccine efficacy against symptomatic infection.
Our results are consistent with studies on immune protection from SARS-CoV-2 infection. Based on our study, we expect that fractional-dose vaccination could provide partial immunity against SARS-CoV-2 and its variants. Our findings provide a theoretical basis for the efficacy of fractional-dose vaccines, serving as reference evidence for implementing fractional dosing vaccine policies in areas facing vaccine shortages and thereby mitigating disease burden. Fractional-dose vaccination could be a viable vaccination strategy comparable to full-dose vaccination and deserves further exploration.
随着能够逃避疫苗和既往感染所产生免疫的 SARS-CoV-2 变异株的出现，疫苗短缺和疫苗有效性给各国政府扩大加强针接种计划带来了前所未有的挑战。疫苗剂量分割可能是帮助社会应对这些挑战的有效策略，因为分剂量可能具有与标准剂量相当的疗效。
本研究旨在通过中和抗体水平研究疫苗免疫原性和保护作用之间的关系，并预测 COVID-19 疫苗分剂量的疗效。
在这项研究中，我们使用了 13 项 COVID-19 疫苗研究和康复队列的数据，分析了体外中和水平与无症状感染和有症状感染观察疗效之间的关系。我们还根据包括在系统评价中的 51 项研究的免疫原性数据，使用中和作用作为中间变量，预测了分剂量的疗效。
与康复水平相比，疫苗对无症状感染和有症状感染的疗效从 8.8%（95%CI，1.4%-16.1%）增加到 71.8%（95%CI，63%-80.7%）和从 33.6%（95%CI，23.6%-43.6%）增加到 98.6%（95%CI，97.6%-99.7%），而平均中和水平从康复水平的 0.1 倍增加到 10 倍。此外，mRNA 疫苗提供了最强的保护，从标准剂量的 50%到 100%，分剂量的保护作用下降缓慢。我们还观察到，尽管疫苗疗效随着平均中和水平的增加而增加，但对于无症状感染的疫苗疗效，这种增加的速度比有症状感染的疫苗疗效要慢。
我们的结果与关于 SARS-CoV-2 感染免疫保护的研究一致。基于我们的研究，我们预计分剂量接种可以提供针对 SARS-CoV-2 及其变体的部分免疫。我们的研究结果为分剂量疫苗的疗效提供了理论依据，为疫苗短缺地区实施分剂量疫苗政策提供了参考证据，从而减轻疾病负担。分剂量接种可能是一种与全剂量接种相当的可行接种策略，值得进一步探索。
