Low-dose yellow fever vaccination in infants: a randomised, double-blind, non-inferiority trial.

In adults, a 500 IU dose has recently been shown to be non-inferior to the full standard dose, but the minimum effective dose for children is unknown.

在成人中，最近的研究显示500 IU剂量与完整标准剂量相比具有非劣效性，但儿童的最小有效剂量尚不明确。

Methods

We conducted a randomised, double-blind, non-inferiority trial at two centres in Kenya and Uganda, including infants aged 9-12 months with no previous yellow fever vaccination or infection.

我们在肯尼亚和乌干达的两个中心进行了一项随机、双盲、非劣效试验，包括9-12个月大且之前未接种过黄热病疫苗或未感染过黄热病的婴儿。

Participants were randomly assigned 1:1 in blocks of variable sizes of four, six, or eight to receive either the standard dose (>13 000 IU) or 500 IU of the Institut Pasteur de Dakar (Dakar, Senegal) 17D-204 yellow fever vaccine, co-administered with the measles-rubella vaccine.

参与者按1:1的比例随机分配，以可变大小的四个、六个或八个为一组，接受标准剂量（>13000 IU）或500 IU的达喀尔巴斯德研究所（塞内加尔，达喀尔）17D-204黄热病疫苗，与麻疹-风疹疫苗联合接种。

The primary outcome was seroconversion 28 days post-vaccination, defined as a four-fold or greater increase in antibody titre at day 28 from baseline (day 0), as measured by the 50% plaque reduction neutralisation test.

主要结果是接种疫苗后28天的血清转换，定义为从基线（第0天）到第28天抗体滴度至少增加四倍，通过50%斑块减少中和试验测量。

Non-inferiority was shown if the lower bound of the 95% CI for the difference in seroconversion rates between doses exceeded -10 percentage points.

如果血清转换率差异的95%置信区间下限超过-10个百分点，则显示非劣效性。

Safety was assessed in the safety population, which included all participants who received a study vaccine dose.

安全性评估是在安全人群中进行的，该人群包括所有接受了研究疫苗剂量的参与者。

This study is registered with ClinicalTrials.gov (NCT04059471) and is complete.

该研究已在ClinicalTrials.gov注册（NCT04059471），研究已完成。

Results

Between Oct 7, 2021, and June 14, 2023, 420 infants were enrolled and randomly assigned (210 participants in each group).

2021年10月7日至2023年6月14日期间，共有420名婴儿被纳入研究并随机分配（每组210名参与者）。

The seroconversion rate at day 28 was 99% (95% CI 96-100; 177 of 179 infants) for the standard dose and 93% (88-96; 166 of 179 infants) for the 500 IU dose in the per-protocol population.

在第28天时，标准剂量组的血清转化率为99%（95%置信区间96-100；179名婴儿中有177名），而500 IU剂量组的血清转化率为93%（95%置信区间88-96；179名婴儿中有166名），这是在符合方案的人群中的数据。

The difference in seroconversion rate was -6·15 percentage points (95% CI -10·27 to -2·02); therefore, non-inferiority was not met for the 500 IU dose. 12 serious adverse events were reported in the study (eight in the 500 IU dose group and four in the standard dose group), but all were considered unrelated to vaccination.

血清转化率的差异为-6.15个百分点（95%置信区间-10.27至-2.02）；因此，500 IU剂量未达到非劣效性标准。研究中报告了12起严重不良事件（500 IU剂量组有八起，标准剂量组有四起），但所有事件均被认为与疫苗接种无关。

interpretation

Compared with the standard yellow fever vaccine dose, a dose of 500 IU did not meet the non-inferiority criterion, suggesting that minimum dose requirements in adults are not generalisable to infants.

与标准黄热病疫苗剂量相比，500 IU剂量未达到非劣效性标准，这表明成人最低剂量要求并不适用于婴儿。

Therefore, standard yellow fever doses should be used for infants in the routine WHO Expanded Programme on Immunization.

因此，在世界卫生组织扩大免疫规划的常规工作中，应为婴儿使用标准的黄热病剂量。

funding

European and Developing Countries Clinical Trials Partnership and the Wellcome Trust.

欧洲和开发中国家临床试验伙伴关系以及威康信托基金。