Immunogenicity of fractional one-fifth and one-half doses of 17DD yellow fever vaccine compared with full dose in children aged 9-23 months in Uganda: a phase 4, single-blind, randomised clinical trial.

However, little evidence still remains in children younger than 2 years.

然而，在2岁以下的儿童中，证据仍然很少。

We assessed immunogenicity of one-fifth (0·1 mL) and one-half (0·25 mL) fractional doses compared with full doses of 17DD yellow fever vaccine in children aged 9-23 months in Kampala, Uganda.

我们在乌干达坎帕拉对9-23个月大的儿童评估了17DD黄热病疫苗的五分之一（0.1毫升）和一半（0.25毫升）分数剂量与全剂量的免疫原性。

Methods

This phase 4, single-blind, randomised clinical trial evaluating fractional dose 17DD yellow fever vaccine among children was conducted at three public-sector health facilities in Uganda.

这项第四阶段、单盲、随机临床试验评估了乌干达三个公共部门卫生设施中9-23个月大儿童的17DD黄热病疫苗分数剂量。

Eligible participants were aged 9-23 months at enrolment, had no history of yellow fever disease or vaccination, and did not meet the exclusion criteria.

符合条件的参与者在入组时年龄为9-23个月，没有黄热病疾病或接种疫苗的历史，且不符合排除标准。

Children were enrolled in three age strata: 9-12 months, 13-18 months, and 19-23 months, and were randomly assigned (1:1:1) using block randomisation (block sizes of three and six) to one-fifth (0·1 mL), one-half (0·25 mL), or full (0·5 mL) doses of the 17DD yellow fever vaccine.

儿童按三个年龄层（9-12个月、13-18个月和19-23个月）进行分层，并使用块随机化（块大小为三和六）随机分配（1:1:1）到17DD黄热病疫苗的五分之一（0.1毫升）、一半（0.25毫升）或全剂量（0.5毫升）。

Participants were followed up at 4 weeks (visit 1 [V1]), 1 year (visit 2 [V2]), and 13-48 months (visit 3 [V3]) after vaccination.

参与者在接种疫苗后4周（访问1 [V1]）、1年（访问2 [V2]）和13-48个月（访问3 [V3]）进行了随访。

The primary analysis included per-protocol participants who attended within the prespecified visit window; an intention-to-treatanalysis was also conducted including all randomly assigned participants with available outcome data.

主要分析包括在预定访问窗口内参加的按方案参与者；还进行了一种意向治疗分析，包括所有有可用结果数据的随机分配参与者。

Participants with missing serological data were excluded from the analysis at the corresponding visit.

在相应访问时，缺失血清学数据的参与者被排除在分析之外。

The primary outcome was non-inferiority in seroconversion (5 percentage-point margin) at V1 measured by 50% plaque reduction neutralisation test.

主要结果是在V1时通过50%斑块减少中和试验测量的血清转化的非劣效性（5个百分点的边界）。

This study is registered with ClinicalTrials.gov, NCT03725618, and is complete.

这项研究已在ClinicalTrials.gov上注册，编号为NCT03725618，并已完成。

Results

Between March 26, 2019, and May 11, 2021, 1784 participants were randomly assigned to either one-fifth dose (n=600), one-half dose (n=594), or full dose (n=590).

从2019年3月26日到2021年5月11日，共有1784名参与者被随机分配到五分之一剂量组（n=600）、一半剂量组（n=594）或全剂量组（n=590）。

The median (IQR) age at enrolment was 13 (11-18) months.

入组时的中位年龄（四分位数间距）为13（11-18）个月。

Both fractional doses met the non-inferiority criterion compared with the full dose with no difference in seroconversion between one-fifth and full doses and -0·17 (95% CI -0·52 to 0·17) difference between one-half and full doses in the per-protocol population at V1.

与全剂量相比，两种分数剂量均满足非劣效性标准，且在V1时，五分之一剂量与全剂量之间在血清转化上没有差异，一半剂量与全剂量之间的差异为-0.17（95%置信区间-0.52至0.17），这是在按方案人群中的结果。

There was no difference between the one-fifth and full doses.

五分之一剂量和全剂量之间没有差异。

interpretation

Both fractional doses of 17DD yellow fever vaccine were non-inferior to full doses in inducing initial seroconversion.

17DD黄热病疫苗的两种分数剂量在诱导初始血清转化方面均不劣于全剂量。

The results support the use of fractional dose yellow fever vaccines among young children for outbreak response during supply shortages.

研究结果支持在供应短缺期间，为应对疫情爆发，对幼儿使用分剂量的黄热病疫苗。

funding

US Centers for Disease Control and Prevention.

美国疾病控制与预防中心。