期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：8
DOI：10.1073/pnas.2116932119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Switching to fractional doses could dramatically accelerate vaccination, and clinical evidence suggests that fractional doses of COVID-19 vaccines could be highly effective. However, there is uncertainty about the effectiveness of fractional doses. In this paper, we present the existing evidence and use epidemiological models to quantify benefits under various scenarios. We argue for more experimental or observational data to be collected urgently. Because switching to fractional dosing could dramatically accelerate vaccination, the potential benefits of further testing of fractional doses far outweigh the costs.
Due to the enormous economic, health, and social costs of the COVID-19 pandemic, there are high expected social returns to investing in parallel in multiple approaches to accelerating vaccination. We argue there are high expected social returns to investigating the scope for lowering the dosage of some COVID-19 vaccines. While existing evidence is not dispositive, available clinical data on the immunogenicity of lower doses combined with evidence of a high correlation between neutralizing antibody response and vaccine efficacy suggests that half or even quarter doses of some vaccines could generate high levels of protection, particularly against severe disease and death, while potentially expanding supply by 450 million to 1.55 billion doses per month, based on supply projections for 2021. An epidemiological model suggests that, even if fractional doses are less effective than standard doses, vaccinating more people faster could substantially reduce total infections and deaths. The costs of further testing alternative doses are much lower than the expected public health and economic benefits. However, commercial incentives to generate evidence on fractional dosing are weak, suggesting that testing may not occur without public investment. Governments could support either experimental or observational evaluations of fractional dosing, for either primary or booster shots. Discussions with researchers and government officials in multiple countries where vaccines are scarce suggests strong interest in these approaches.
