DataSheet_1_Safety and immunogenicity of a modified Omicron-adapted inactivated vaccine in healthy adults: a randomized, double-blind, active-controlled Phase III clinical trial.docx

BackgroundUpdated vaccine strategies are needed to protect against new SARS-CoV-2 variants with increased immune escape. Here, information on the safety and immunogenicity of an inactivated Omicron-adapted vaccine is presented, as compared with CoronaVac.
MethodsA randomized, double-blind, active-controlled, phase III clinical trial was conducted to compare a modified Omicron-adapted vaccine (Omicron vaccine) with the authorized prototype vaccine (CoronaVac®) as a booster dose. Healthy adults aged ≥18 years, who have previously received 2 or 3 doses of CoronaVac (2C or 3C cohort) at least 6 months before, were enrolled to get a booster dose of Omicron vaccine or CoronaVac in a ratio of 2:1 (2C/3C+1O/1C). Back-up serums after two initial doses of CoronaVac (2C+0) for adults aged 26-45 years were collected from a previous study. Immunogenicity and safety data at 28 days after vaccination were collected and analyzed. One of the primary objectives was to evaluate the superiority of immunogenicity of Omicron vaccine booster against Omicron BA.1, compared with CoronaVac booster against BA.1. Another objective was to evaluate the non-inferiority of immunogenicity of Omicron vaccine booster against BA.1, compared with two initial doses of CoronaVac against ancestral strain.
ResultsBetween June 1st and July 21st, 2022, a total of 1,500 healthy adults were enrolled. Results show that all pre-specified superiority criteria for BA.1 neutralizing antibody were met. Specifically, within the 3C cohort (3C+1O vs. 3C+1C), the geometric mean titers’ (GMT) ratio and 95% confidence interval (CI) was 1.64 (1.42, 1.89), with the lower 95%CI ≥1; a GMT ratio of 1.84 (1.57, 2.16) was observed for 2C+1O versus 3C+1C. For seroconversion rate, the lower 95%CIs of differences between immuno-comparative groups (2/3C+1O vs. 3C+1C) were all above the superiority criterion 0%. However, the non-inferiority criterion of the lower 95%CI of GMT ratio ≥2/3 was unfulfilled for 2C/3C+1O against BA.1 versus 2C+0 against ancestral strain. Safety profiles were similar between groups, with no safety concerns identified.
ConclusionThe Omicron-adapted vaccine was well-tolerated and could elicit superior immune responses as compared with CoronaVac against Omicron, while it appeared inferior to CoronaVac against ancestral strain.
Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT05381350?term=NCT05381350&draw=2&rank=1, identifier NCT05381350.

背景 亟需更新疫苗策略以对抗免疫逃逸能力增强的新型SARS-CoV-2变异株。本研究报道了奥密克戎适配灭活疫苗（Omicron-adapted vaccine）与克尔来福（CoronaVac®）的安全性及免疫原性数据。
方法 本研究为一项随机、双盲、阳性对照的III期临床试验，旨在比较改良型奥密克戎适配疫苗（下称奥密克戎疫苗）作为加强针与已获批原型毒株疫苗克尔来福®的差异。纳入标准为：既往至少6个月前已完成2剂或3剂克尔来福接种（分别记为2C队列、3C队列）的≥18岁健康成人，以2:1的比例随机接种奥密克戎疫苗加强针或克尔来福加强针（分组方式为2C/3C+1O/1C）。此外，从既往研究中收集26-45岁成人完成2剂克尔来福初始接种后（2C+0组）的备用血清样本。本研究收集并分析了接种后28天的免疫原性与安全性数据。本研究的主要终点之一为：相较于克尔来福加强针针对奥密克戎BA.1株的免疫原性，奥密克戎疫苗加强针针对BA.1株的免疫原性更具优效性；另一终点为：相较于2剂初始克尔来福接种针对原始毒株的免疫原性，奥密克戎疫苗加强针针对BA.1株的免疫原性满足非劣效性要求。
结果 2022年6月1日至7月21日期间，共纳入1500名健康成人。研究结果显示，所有针对BA.1株中和抗体的预设优效性标准均已达成。具体而言，在3C队列（3C+1O组 vs 3C+1C组）中，几何平均滴度（geometric mean titers, GMT）比值及其95%置信区间（confidence interval, CI）为1.64（95%CI: 1.42, 1.89），其95%置信区间下限≥1；在2C+1O组 vs 3C+1C组中，GMT比值为1.84（95%CI: 1.57, 2.16）。针对血清阳转率，各免疫比较组（2/3C+1O组 vs 3C+1C组）的组间差值的95%置信区间下限均高于优效性阈值0%。但奥密克戎疫苗加强针针对BA.1株的GMT比值的95%置信区间下限未达到≥2/3的非劣效性标准（与2C+0组针对原始毒株的免疫原性对比）。各组安全性特征相似，未发现新的安全隐患。
结论 奥密克戎适配疫苗耐受性良好，相较于克尔来福，其可诱导针对奥密克戎变异株更优的免疫应答，但针对原始毒株的免疫原性似乎弱于克尔来福。
临床试验注册：https://classic.clinicaltrials.gov/ct2/show/NCT05381350?term=NCT05381350&draw=2&rank=1，试验识别号NCT05381350。