健康成年人中改良的奥密克戎适应灭活疫苗的安全性和免疫原性：一项随机、双盲、阳性对照的 III 期临床研究。
Safety and immunogenicity of a modified Omicron-adapted inactivated vaccine in healthy adults: a randomized, double-blind, active-controlled Phase III clinical trial.
机构信息
Department of Vaccine Clinical Evaluation, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China.
Division of Respiratory Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control, Beijing, China.
出版信息
Front Immunol. 2023 Sep 18;14:1241153. doi: 10.3389/fimmu.2023.1241153. eCollection 2023.
BACKGROUND
Updated 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.
METHODS
A 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.
RESULTS
Between June 1 and July 21, 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.
CONCLUSION
The 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 REGISTRATION
https://classic.clinicaltrials.gov/ct2/show/NCT05381350?term=NCT05381350&draw=2&rank=1, identifier NCT05381350.
背景
需要更新疫苗策略以预防具有更高免疫逃逸能力的新型 SARS-CoV-2 变体。本文介绍了一种灭活的奥密克戎适应疫苗的安全性和免疫原性，与科兴疫苗相比。
方法
一项随机、双盲、主动对照、III 期临床试验比较了改良的奥密克戎适应疫苗（Omicron 疫苗）与已授权的原型疫苗（科兴疫苗）作为加强针。至少在 6 个月前接受过 2 或 3 剂科兴疫苗（2C 或 3C 队列）的≥18 岁健康成年人按 2:1（2C/3C+1O/1C）的比例接受奥密克戎疫苗或科兴疫苗的加强针。此前一项研究中，为 26-45 岁的成年人收集了初次接种 2 剂科兴疫苗（2C+0）后的备份血清。接种后 28 天收集并分析免疫原性和安全性数据。主要目标之一是评估奥密克戎疫苗加强针针对奥密克戎 BA.1 的免疫原性优于科兴疫苗加强针针对 BA.1 的免疫原性。另一个目标是评估奥密克戎疫苗加强针针对 BA.1 的免疫原性与两剂科兴疫苗针对原始株的非劣效性。
结果
2022 年 6 月 1 日至 7 月 21 日期间，共纳入 1500 名健康成年人。结果表明，所有针对 BA.1 中和抗体的预先指定优势标准均得到满足。具体而言，在 3C 队列（3C+1O 与 3C+1C）中，几何平均滴度（GMT）比值和 95%置信区间（CI）为 1.64（1.42，1.89），置信区间下限（CI）≥1；观察到 2C+1O 与 3C+1C 的 GMT 比值为 1.84（1.57，2.16）。对于血清转化率，免疫比较组（2/3C+1O 与 3C+1C）之间差异的置信区间下限（CI）均高于优势标准 0%。然而，2C/3C+1O 对 BA.1 的 GMT 比值的置信区间下限（CI）≥2/3 的非劣效性标准未得到满足。与两剂科兴疫苗（2C+0）相比，奥密克戎疫苗对原始株的免疫原性似乎不如科兴疫苗。
安全性概况在各组之间相似，未发现安全性问题。
结论
与科兴疫苗相比，奥密克戎适应疫苗具有良好的耐受性，并能引发针对奥密克戎的更高免疫反应，而与科兴疫苗针对原始株的免疫反应相比，奥密克戎适应疫苗似乎较差。
临床试验注册
https://classic.clinicaltrials.gov/ct2/show/NCT05381350?term=NCT05381350&draw=2&rank=1，标识符 NCT05381350。
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