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[转载]科兴新冠病毒灭活疫苗第三剂(加强针)后中和抗体水平显著增高

已有 3842 次阅读 2021-7-26 19:49 |系统分类:论文交流|文章来源:转载

2021年7月25日,由江苏省疾病预防控制中心疫苗评价所联合复旦大学公卫学院、科兴生物公司(SINOVAC)、复旦大学附属华山医院等多家单位合作,在健康科学预印本论文平台Medrxiv上传了题为“Immunogenicity and safety of a third dose, and immune persistence of CoronaVac vaccine in healthy adults aged 18-59 years: interim results from a double-blind, randomized, placebo-controlled phase 2 clinical trial”《18-59岁健康成年人接种克尔来福®第三剂的免疫原性和安全性,以及免疫持久性:双盲、随机、安慰剂对照的Ⅱ期临床试验中期结果》的文章。这是国产疫苗首个加强针的II期临床试验结果。研究结果显示,接种两剂SINOVAC科兴公司新冠灭活疫苗尔来福后可产生良好的免疫记忆,在接种第二剂后的第28天至8个月接种第三剂后,中和抗体水平显著高于基线水平,不良事件均为1级或2级,未出现相关的严重不良反应。研究结果表明,接种两剂克尔来福®后具有良好的免疫原性,且能够诱导机体产生免疫记忆;第三剂灭活疫苗接种后具有良好的免疫原性和安全性

  本次研究是单中心、双盲、随机、安慰剂对照的克尔来福®Ⅱ期临床研究,于2020年5月3日在中国江苏启动。受试者为18-59岁的健康成人,共271人纳入最终分析。入组受试者被划分为四个免疫程序组(第1-4组):第1组在第0,14,42天各接种1剂克尔来福®;第2组在第0,14,254天各接种1剂克尔来福®;第3组在第0,28,56天各接种1剂克尔来福®;第4组在第0,28,268天各接种1剂克尔来福®。各组受试者的平均年龄为44.1岁、40.8岁、41.2岁、42.2岁。女性(53.8%)略多于男性。


  免疫原性分析显示,四个免疫程序组在第二或第三剂接种后28天中和抗体阳性率均在90.0%以上。安全性分析显示,在各个免疫程序组中,第三剂后28天内报告的局部和全身不良反应略低于前两剂,均为1级2级不良反应,最常见的不良反应是注射部位疼痛。未报告严重不良反应。


  该研究结果也表明,尽管6个月后中和抗体水平下降,但两剂疫苗免疫程序产生了良好的免疫记忆,接种第三剂后能够迅速诱导强烈的免疫反应,中和抗体滴度显著提高,接种第三剂后28天中和抗体滴度比第二剂后28天中和抗体滴度增加了3-5倍,且第三剂与第二剂间隔时间越长,增长倍数越高。

科兴灭活三针.jpg

 Figure 2. Level of neutralizing antibodies to live SARS-CoV-2 in 3 μg group: A)-B)days 0 and 14 vaccination cohort; C)-D) days 0 and 28 vaccination cohortNote: Data are represented as reciprocal neutralizing antibody titers regarding the time after the first dose in per-protocol population. Numbers above the bars show the Geometric Mean Titer (GMT), and the error bars indicate the 95% CI. Statistical differences were assessed by t-test on log-transformed data.

接种方案:
-第1组:第0-14-42天接种疫苗;
-第2组:第0-14-194天接种疫苗;
-第3组:第0-28-56天接种疫苗;
-第4组:第0-28–208天接种疫苗。


接种第三针有效,有效诱导出高水平的中和抗体:

-第1组(0-14-42)的第三针打完第28天,中和抗体GMT达到45.6,然而在半年之后又跌到9.2;

-第2组(0-14-194)的第三针打完第28天,中和抗体GMT达到137.9;

-第3组(0-28-56)的第三针打完第28天,中和抗体GMT达到49.7;

-第4组(0-28–208)的第三针打完第28天,中和抗体GMT达到143.1。


   虽然有着显著下降,但由于前两针已经产生足够强的免疫记忆,第三针疫苗可以唤醒记忆B细胞,诱导出强烈的体液免疫应答,中和抗体水平显著提高。间隔6个月比间隔2~4周接种第三针灭活疫苗,诱导的中和抗体水平更高。


   在讨论部分作者表示,尽管第三剂接种可能是必不可少的,但制定和实施加强方案应综合考虑当地的疾病流行情况、感染风险、疫苗供应等相关因素。根据当前形势,从中短期来看,与加强剂次接种相比,确保更多的人完成两剂克尔来福®接种应该是更优先事项。


以上转自科兴生物官方——疫苗之益微信公众号。



原文摘要:Abstract

Background: Large-scale vaccination is being implemented globally with CoronaVac, an inactivated vaccine against coronavirus disease 2019 (COVID-19). Immunogenicity and safety profiles of homologous two-dose schedules have been published. We report interim results of immune persistence, and the immunogenicity and safety of a third dose of CoronaVac. Methods In this ongoing, placebo-controlled, double-blind phase 2 trial in 18-to-59-year-olds, we randomly assigned subjects, 1:1:1:1, to one of four schedules to receive a third dose, 28 days or 6 months after two two-dose regimens (14-day or 28-day apart): schedule 1: days 0, 14, 42; schedule 2: days 0, 14, 194; schedule 3: days 0, 28, 56; schedule 4: days 0, 28, 208. For each schedule, participants were randomly assigned to either a medium-dose group (3 μg per 0.5 mL of aluminum hydroxide diluent per dose), a high-dose group (6 μg), or a placebo group (2:2:1). The primary outcome was geometric mean titers (GMTs) of neutralizing antibody to live SARS-CoV-2. Results Overall, 540 participants received a third dose. In the 3 μg group, neutralizing antibody titers induced by the first two doses declined after 6-8 months to below the seropositive cutoff (GMT: 4.1 [95%CI 3.3-5.2] for Schedule 2 and 6.7 [95%CI 5.2-8.6] for Schedule 4). When a third dose was given 6-8 months after a second dose, GMTs assessed 14 days later increased to 137.9 [95%CI 99.9-190.4] for Schedule 2, and 143.1 [95%CI 110.8-184.7] for Schedule 4, approximately 3-fold above Schedule 1 and Schedule 3 GMTs after third doses. Similar patterns were observed for the 6 μg group. The severity of solicited local and systemic adverse reactions reported within 28 days after the third dose were grade 1 to grade 2 in all vaccination cohorts. None of the fourteen serious adverse events were considered to be related to vaccination. Conclusions A third dose of CoronaVac administered 6 or more months after a second dose effectively recalled specific immune response to SARS-CoV-2, resulting in a remarkable increase in antibody levels, and indicating that a two-dose schedule generates good immune memory. Optimizing the timing of a booster dose should take into account immunogenicity, vaccine efficacy/effectiveness, local epidemic situation, infection risk, and vaccine supply. 


参考文献:

 Immunogenicity and safety of a third dose, and immune persistence of CoronaVac vaccine in healthy adults aged 18-59 years: interim results from a double-blind, randomized, placebo-controlled phase 2 clinical trial. doi: https://doi.org/10.1101/2021.07.23.21261026 

原文网址:https://www.medrxiv.org/content/10.1101/2021.07.23.21261026v1 





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