PDF(Pubmed)
Abstract：
Continuous emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enhanced transmissibility, significant immune escape, and waning immunity call for booster vaccination. We evaluated the safety, immunogenicity, and efficacy of heterologous booster with a SARS-CoV-2 mRNA vaccine SYS6006 versus an active control vaccine in a randomized, open-label, active-controlled phase 3 trial in healthy adults aged 18 years or more who had received two or three doses of SARS-CoV-2 inactivated vaccine in China. The trial started in December 2022 and lasted for 6 months. The participants were randomized (overall ratio: 3:1) to receive one dose of SYS6006 (N = 2999) or an ancestral receptor binding region-based, alum-adjuvanted recombinant protein SARS-CoV-2 vaccine (N = 1000), including 520 participants in an immunogenicity subgroup. SYS6006 boosting showed good safety profiles with most AEs being grade 1 or 2, and induced robust wild-type and Omicron BA.5 neutralizing antibody response on Days 14 and 28, demonstrating immunogenicity superiority versus the control vaccine and meeting the primary objective. The relative vaccine efficacy against COVID-19 of any severity was 51.6% (95% CI, 35.5-63.7) for any variant, 66.8% (48.6-78.5) for BA.5, and 37.7% (2.4-60.3) for XBB, from Day 7 through Month 6. In the vaccinated and infected hybrid immune participants, the relative vaccine efficacy was 68.4% (31.1-85.5) against COVID-19 of any severity caused by a second infection. All COVID-19 cases were mild. SYS6006 heterologous boosting demonstrated good safety, superior immunogenicity and high efficacy against BA.5-associated COVID-19, and protected against XBB-associated COVID-19, particularly in the hybrid immune population.Trial registration: Chinese Clinical Trial Registry: ChiCTR2200066941.
摘要：
不断出现严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的新变种，增强的可传播性，显著的免疫逃逸，免疫力下降需要加强疫苗接种。我们评估了安全性，免疫原性,SARS-CoV-2mRNA疫苗SYS6006与活性对照疫苗的异源性加强剂在随机，开放标签，在中国接受过两剂或三剂SARS-CoV-2灭活疫苗的18岁或以上健康成年人中进行的积极对照3期试验。该试验于2022年12月开始，持续了6个月。参与者被随机分配（总体比例：3：1）接受一剂SYS6006（N=2999）或基于祖先受体结合区的剂量，明矾佐剂重组蛋白SARS-CoV-2疫苗（N=1000），包括520名免疫原性亚组参与者。SYS6006加强显示出良好的安全性特征,其中大多数AE为1级或2级,并且在第14天和第28天诱导出稳健的野生型和OmicronBA.5中和抗体应答,显示出相对于对照疫苗的免疫原性优势并满足主要目标。针对任何严重程度的COVID-19，任何变体的相对疫苗效力为51.6%(95%CI，35.5-63.7)，BA.5为66.8%（48.6-78.5），XBB为37.7%（2.4-60.3），从第7天到第6个月。在接种疫苗和感染的混合免疫参与者中，对于由二次感染引起的任何严重程度的COVID-19，相对疫苗有效率为68.4%(31.1-85.5)。所有COVID-19病例均为轻度。SYS6006异源加强显示良好的安全性，对BA.5相关COVID-19具有优异的免疫原性和高效力，并对XBB相关COVID-19具有保护作用，特别是在杂交免疫群体中。试验注册:中国临床试验注册中心:ChiCTR2200066941。
