肯尼亚医学研究所George M. Warimwe团队研究了非洲成人低剂量黄热病疫苗的效果。这一研究成果于2025年2月20日发表在《新英格兰医学杂志》上。

黄热病疫苗单剂非常有效，但疫苗供应有限。血清转化所需的最低剂量仍然未知。

在乌干达和肯尼亚进行的这项双盲、随机、非劣效性试验中，研究组分配了没有黄热病疫苗接种史或感染史的成年人接受达喀尔巴斯德研究所17D-204黄热病疫苗的标准剂量（13803 IU）或1000 IU、500 IU或250 IU的分次剂量接种。主要结局是接种后28天的血清转化，与标准剂量进行比较，在非劣效性分析中进行评估。血清转化被定义为第28天的抗体滴度至少是接种前抗体滴度的四倍，通过斑块减少中和试验测量。按照方案和意向治疗人群进行非劣效性分析。如果分剂量和标准剂量之间血清转化发生率差异的95%置信区间的下限高于-10个百分点，则表明非劣效性。

共有480名参与者接受了随机分组（每组120名参与者）。使用标准剂量时，血清转化率为98%（95%置信区间[CI]，94至100）。在意向治疗人群中，1000-IU剂量和标准剂量之间的血清转化率差异为0.01个百分点（95%CI，-5.0至5.1），在符合方案的人群中为-1.9个百分点（95%CI，-7.0至3.2）；500-IU剂量和标准剂量之间的相应差异分别为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-IU剂量与标准剂量的相应差异为-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例疫苗相关不良事件：103例为轻度，7例为中度，1例为重度。四组的不良事件发生率相似。

研究结果表明，低至500 IU的黄热病疫苗剂量在28天内产生的血清转化率不低于13803 IU的标准剂量。

附：英文原文

Title: Low-Dose Yellow Fever Vaccine in Adults in Africa

Author: Derick Kimathi, Aitana Juan-Giner, Ndeye S. Bob, Benedict Orindi, Maria L. Namulwana, Antoine Diatta, Stanley Cheruiyot, Gamou Fall, Moussa Dia, Mainga M. Hamaluba, Dan Nyehangane, Henry K. Karanja, John N. Gitonga, Daisy Mugo, Donwilliams O. Omuoyo, Mwatasa Hussein, Elizaphan Oloo, Naomi Kamau, Jackline Wafula, Josephine Bendera, Namanya Silvester, James Mwavita, Musiimenta Joshua, Jane Mwendwa, Collins Agababyona, Caroline Ngetsa, Nalusaji Aisha, Felix Moki, Titus Buluku, Marianne Munene, Juliet Mwanga-Amumpaire, Julius Lutwama, John Kayiwa, Eunice Kamaara, Alan D. Barrett, Pontiano Kaleebu, Philip Bejon, Amadou A. Sall, Rebecca F. Grais, George M. Warimwe

Issue&Volume: 2025-02-20

Abstract:

BACKGROUND

Yellow fever vaccine is highly effective with a single dose, but vaccine supply is limited. The minimum dose requirements for seroconversion remain unknown.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

DOI: NJ202502203920809

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2407293