Immunogenicity and Safety of vYF, a Yellow Fever Vaccine - A Phase 2 Trial.

The safety of and immune response to vYF as compared with those of the licensed yellow fever vaccine, YF-VAX, are unclear.

vYF疫苗的安全性和免疫反应与已获许可的黄热病疫苗YF-VAX相比尚不明确。

Methods

In this year 1 interim analysis of a phase 2, observer-blinded, randomized, active-controlled trial, we randomly assigned healthy adults 18 to 60 years of age in a 2:1 ratio to receive vYF or YF-VAX as a single vaccine injection on day 1.

在这项为期2年、观察者盲法、随机、活性对照的第1年中期分析的2期临床试验中，我们按照2:1的比例，随机分配了18至60岁的健康成年人，分别接受vYF或YF-VAX作为第1天的单一疫苗注射。

Neutralizing antibody titers were measured on day 29, month 6, and year 1.

中和抗体滴度在第29天、第6个月和第1年进行测量。

The primary analysis focused on the per-protocol population, which included participants with no history of yellow fever infection or vaccination and with no protocol deviations.

主要分析集中在符合方案人群，包括没有黄热病感染或接种疫苗史且没有方案偏离的参与者。

Noninferiority would be shown if the lower limit of the two-sided 95% confidence intervalof the between-group difference in the percentage of participants with seroconversion was greater than -5 percentage points on day 29.

如果在第29天，两组间血清转化率差异的双侧95%置信区间下限大于-5个百分点，则表明非劣效性。

Results

A total of 568 participants were enrolled: 382 in the vYF group and 186 in the YF-VAX group; 329 and 156 participants, respectively, were included in the per-protocol population for the noninferiority analysis.

共有568名参与者被纳入研究：其中382名在vYF组，186名在YF-VAX组；分别有329名和156名参与者被纳入非劣效分析的按方案人群。

Seroconversion by day 29 occurred in 99.7% of participants receiving vYF and 99.4% of those receiving YF-VAX (difference, 0.3 percentage points; 95% confidence interval, -1.2 to 3.2, which met the criterion for noninferiority).

在第29天，vYF组的99.7%和YF-VAX组的99.4%的参与者发生了血清转换（差异为0.3个百分点；95%置信区间为-1.2至3.2，满足非劣效标准）。

Neutralizing antibody geometric mean titers were similar in the two vaccine groups, peaking on day 29 (in the vYF group, 1:2654 among participants with no history of yellow fever infection or vaccination and 1:1312 among participants with a history of yellow fever infection or vaccination; in the YF-VAX group, 1:3147 and 1:1079, respectively), then decreasing through 1 year after vaccination (in the vYF group, 1:401 among participants with no history of yellow fever infection or vaccination and 1:490 among participants with a history of yellow fever infection or vaccination; in the YF-VAX group, 1:548 and 1:646, respectively).

中和抗体几何平均滴度在两组疫苗接种者中相似，在接种后第29天达到高峰（在vYF组中，无黄热病感染或接种史的参与者为1:2654，有黄热病感染或接种史的参与者为1:1312；在YF-VAX组中，分别为1:3147和1:1079），然后在接种后1年内逐渐下降（在vYF组中，无黄热病感染或接种史的参与者为1:401，有黄热病感染或接种史的参与者为1:490；在YF-VAX组中，分别为1:548和1:646）。

No major safety concerns were identified.

未发现主要的安全问题。

The safety profiles were similar in the two vaccine groups: solicited adverse events were reported by 208 of 367 participants (56.7%) in the vYF group and 113 of 185 participants (61.1%) in the YF-VAX group, and unsolicited adverse events were reported by 99 of 379 participants (26.1%) and 39 of 186 participants (21.0%), respectively.

在两组疫苗中，安全性特征相似：在vYF组的367名参与者中有208人（56.7%）报告了主动不良事件，在YF-VAX组的185名参与者中有113人（61.1%）报告了主动不良事件；在vYF组的379名参与者中有99人（26.1%）报告了非主动不良事件，在YF-VAX组的186名参与者中有39人（21.0%）报告了非主动不良事件。

Conclusions

In this trial, vYF had immunogenicity and safety profiles similar to those of YF-VAX.

在这项试验中，vYF的免疫原性和安全性特征与YF-VAX相似。

(Funded by Sanofi; ClinicalTrials.gov number, NCT04942210.).

(由赛诺菲资助; ClinicalTrials.gov 注册号, NCT04942210.)。