Kimathi Derick, Juan-Giner Aitana, Bob Ndeye S, Orindi Benedict, Namulwana Maria L, Diatta Antoine, Cheruiyot Stanley, Fall Gamou, Dia Moussa, Hamaluba Mainga M, Nyehangane Dan, Karanja Henry K, Gitonga John N, Mugo Daisy, Omuoyo Donwilliams O, Hussein Mwatasa, Oloo Elizaphan, Kamau Naomi, Wafula Jackline, Bendera Josephine, Silvester Namanya, Mwavita James, Joshua Musiimenta, Mwendwa Jane, Agababyona Collins, Ngetsa Caroline, Aisha Nalusaji, Moki Felix, Buluku Titus, Munene Marianne, Mwanga-Amumpaire Juliet, Lutwama Julius, Kayiwa John, Kamaara Eunice, Barrett Alan D, Kaleebu Pontiano, Bejon Philip, Sall Amadou A, Grais Rebecca F, Warimwe George M
Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
Epicentre, Paris.
N Engl J Med. 2025 Feb 20;392(8):788-797. doi: 10.1056/NEJMoa2407293.
Yellow fever vaccine is highly effective with a single dose, but vaccine supply is limited. The minimum dose requirements for seroconversion remain unknown.
In this double-blind, randomized, noninferiority trial in Uganda and Kenya, we assigned adults with no history of yellow fever vaccination or infection to receive vaccination with the Institut Pasteur de Dakar 17D-204 yellow fever vaccine at a standard dose (13,803 IU) or at a fractional dose of 1000 IU, 500 IU, or 250 IU. The primary outcome was seroconversion at 28 days after vaccination with each fractional dose as compared with the standard dose, evaluated in a noninferiority analysis. Seroconversion was defined as an antibody titer at day 28 that was at least four times as high as the antibody titer before vaccination, as measured by a plaque reduction neutralization test. We conducted noninferiority analyses in the per-protocol and intention-to-treat populations. Noninferiority was shown if the lower boundary of the 95% confidence interval for the difference in the incidence of seroconversion between the fractional dose and the standard dose was higher than -10 percentage points.
A total of 480 participants underwent randomization (120 participants in each group). The incidence of seroconversion was 98% (95% confidence interval [CI], 94 to 100) with the standard dose. The difference in the incidence of seroconversion between the 1000-IU dose and the standard dose was 0.01 percentage points (95% CI, -5.0 to 5.1) in the intention-to-treat population and -1.9 percentage points (95% CI, -7.0 to 3.2) in the per-protocol population; the corresponding differences between the 500-IU dose and the standard dose were 0.01 percentage points (95% CI, -5.0 to 5.1) and -1.8 percentage points (95% CI, -6.7 to 3.2), and those between the 250-IU dose and the standard dose were -4.4 percentage points (95% CI, -9.4 to 0.7) and -6.7 percentage points (95% CI, -11.7 to 1.6). A total of 111 vaccine-related adverse events were reported: 103 were mild in severity, 7 were moderate, and 1 was severe. The incidence of adverse events was similar in the four groups.
A yellow fever vaccination dose as low as 500 IU was noninferior to the standard dose of 13,803 IU for producing seroconversion within 28 days. (Funded by the European and Developing Countries Clinical Trials Partnership and the Wellcome Trust; NIFTY ClinicalTrials.gov number, NCT04059471.).
黄热病疫苗单剂接种就非常有效，但疫苗供应有限。血清转化的最低剂量要求尚不清楚。
在乌干达和肯尼亚进行的这项双盲、随机、非劣效性试验中，我们将无黄热病疫苗接种史或感染史的成年人随机分为接受达喀尔巴斯德研究所17D - 204黄热病疫苗标准剂量（13,803国际单位）或1000国际单位、500国际单位或250国际单位的分剂量接种。主要结局是与标准剂量相比，各分剂量接种后28天的血清转化情况，通过非劣效性分析进行评估。血清转化定义为接种后第28天的抗体滴度至少是接种前抗体滴度的四倍，通过蚀斑减少中和试验测量。我们在符合方案人群和意向性分析人群中进行了非劣效性分析。如果分剂量与标准剂量血清转化发生率差异的95%置信区间下限高于 - 10个百分点，则表明具有非劣效性。
共有480名参与者被随机分组（每组120名参与者）。标准剂量组的血清转化率为98%（95%置信区间[CI]，94至100）。在意向性分析人群中，1000国际单位剂量组与标准剂量组血清转化率的差异为0.01个百分点（95%CI， - 5.0至5.1），在符合方案人群中为 - 1.9个百分点（95%CI， - 7.0至3.2）；500国际单位剂量组与标准剂量组的相应差异分别为0.01个百分点（95%CI， - 5.0至5.1）和 - 1.8个百分点（95%CI， - 6.7至3.2），250国际单位剂量组与标准剂量组的差异分别为 - 4.4个百分点（95%CI， - 9.4至0.7）和 - 6.7个百分点（95%CI， - 11.7至1.6）。共报告了111例与疫苗相关的不良事件：103例为轻度，7例为中度，1例为重度。四组不良事件的发生率相似。
黄热病疫苗接种剂量低至500国际单位在28天内产生血清转化方面不劣于13,803国际单位的标准剂量。（由欧洲和发展中国家临床试验合作组织及惠康信托基金资助；NIFTY临床试验注册号，NCT04059471。）
