目的:评估5-11岁泰国儿童中CoronaVac的异源COVID-19初次疫苗接种方案的免疫原性和安全性。
方法:这种前瞻性,多中心,双盲,随机对照试验将参与者分为1:1:1:1,以接受第二剂标准(10-μg)或半剂量(5-μg)BNT162b2疫苗,如下:CoronaVac/10-μg-BNT162b2(第1组),CoronaVac/5-μg-BNT162b2(第2组),10-μg-BNT162b2/10-μg-BNT162b2(第3组),或10-μg-BNT162b2/5-μg-BNT162b2(第4组)。来自每个手臂的一部分参与者在第二次疫苗接种后16周接受10μg-BNT162b2加强剂(第三)。评估体液和细胞免疫原性,并以数字方式自我报告不良事件(AE)。
结果:在553名注册参与者中,50%是男性,中位数(四分位距)年龄为8.65(7.00,10.00)岁,大多数(91%)的身高体重正常。在第二次接种疫苗两周后,所有参与者都表现出类似的针对祖先武汉毒株的强中和抗体(NAb)。第1组的滴度最高(737.60,95%CI[654.80,830.88]),其次是第3组(630.42,95%CI[555.50,715.45]),2(593.98,95%CI[506.02,697.23]),和4(451.79,95%CI[388.62,525.23]),BA.1和BA.5的血清转化率分别为56.01%和49.68%。与它们各自的全剂量方案相比,半剂量BNT162b2作为第二剂量诱导显著更低的NAb滴度(对于组1对2,p=0.03,对于组3对4,p<0.001)。77.71%的参与者在第二次疫苗接种后两周出现了SARS-CoV-2祖先刺突蛋白特异性T细胞反应。这在手臂上是相似的。加强剂量产生的NAb滴度比针对BA的第二次疫苗接种高5.69-11.51倍。不同手臂的AE相似,所有轻度或中度,并在2-3天后完全解决。
结论:CoronaVac-BNT162b2的标准和部分异源方案比同源BNT162b2诱导相似或更高的体液免疫,代表儿童的替代疫苗方案。这些发现在同时使用两种疫苗的环境中高度相关。
To evaluate immunogenicity and safety of heterologous COVID-19 primary vaccination regimens of CoronaVac with fractional and standard BNT162b2 dosages in 5-11-year-old Thai children.
This prospective, multicenter, double-blind, randomized control trial divided participants 1:1:1:1 to receive a second dose of either standard (10-μg) or half-dose (5-μg) BNT162b2 vaccines as follows: CoronaVac/10-μg-BNT162b2 (Group 1), CoronaVac/5-μg-BNT162b2 (Group 2), 10-μg-BNT162b2/10-μg-BNT162b2 (Group 3), or 10-μg-BNT162b2/5-μg-BNT162b2 (Group 4). A subset of participants from each arm received 10-μg-BNT162b2 booster (third) doses 16 weeks after their second vaccination. Humoral and cellular immunogenicity were assessed and adverse events (AEs) digitally self-reported.
Of 553 enrolled participants, 50 % were male, the median (interquartile range) age was 8.65 (7.00, 10.00) years, and a majority (91 %) had normal weight-for-height. All participants exhibited similarly robust neutralizing antibodies (NAb) against the ancestral Wuhan strain two weeks after the second vaccination, with titers highest in Group 1 (737.60, 95% CI [654.80, 830.88]), followed by Groups 3 (630.42, 95% CI [555.50, 715.45]), 2 (593.98, 95% CI [506.02, 697.23]), and 4 (451.79, 95% CI [388.62, 525.23]), as well as 56.01 % and 49.68 % seroconversion for BA.1 and BA.5, respectively. Half-dose BNT162b2 as a second dose induced significantly lower NAb titers compared to their respective full-dose regimens (p = 0.03 for Groups 1 vs 2 and p < 0.001 for Groups 3 vs 4). 77.71 % of participants developed SARS-CoV-2 ancestral spike protein-specific T-cell responses two weeks after the second vaccination. This was similar across arms. Booster doses generated NAb titers 5.69-11.51-folds higher than the second vaccination against BA.1. AEs were similar across arms, all mild or moderate, and fully resolved 2-3 days thereafter.
Standard and fractional heterologous regimens of CoronaVac-BNT162b2 induced similar or higher humoral immunity than homologous BNT162b2 and represent alternative vaccine regimens for children. These findings are highly relevant in settings concurrently using both vaccines.