Assessment of antibody titer after third doses of COVID-19 mRNA vaccination in healthy volunteers
Assessment of antibody titer after third doses of COVID-19 mRNA vaccination in healthy volunteers
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健康志愿者接种第三剂 COVID-19 mRNA 疫苗后抗体滴度评估
DOI：
10.1515/labmed-2022-0008
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发表时间：
2022
影响因子：
1.2
通讯作者：
Shinichirou Takahashi
中科院分区：
文献类型：
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作者：
Rikei Kozakai;Kuniko Hoshi;Yoshihiko Izumi;Shinichirou Takahashi
截至2022年1月底，严重急性呼吸综合征冠状病毒-2(SARS-CoV-2)已在全球感染超过3.51亿人，造成560多万人死亡。在2021年，包括我们在内的许多群体报告了在接种两剂BNT162b2疫苗后的体液反应和副作用[1-4]。随后，日本从2021年12月1日起刚刚开始第三针SARS-CoV-2疫苗接种。目前，几个小组已经开始报告第三次接种疫苗后的体液反应，表明第三次接种的效果[5-7]。然而，需要进一步的研究来验证这些发现。我们小组最近报告了两剂BNT162b2疫苗接种后的抗体滴度和副作用[4]，以及第一次接种6个月后抗体下降的后续研究[8]。在本研究中，我们检测了东北医科大学医院的健康志愿者在第三次接种辉瑞/BioNTechBNT162b2mRNA疫苗前后的SARS-CoV-2抗体水平。使用新建立的高灵敏度、全自动化学发光酶免疫分析法(CLEIA)评估抗体效价，CLEIA专用于检测针对SARS-CoV-2刺突蛋白受体结合域(RBD)的免疫球蛋白和免疫球蛋白，如所述[4，8]。在本院接受两剂BNT162b2治疗的41名志愿者中，均在第一剂BNT162b2后完成9个月的随访。在编写本报告时，所有41名参与者都已完成这一阶段，在第三次接种疫苗之前或第三次接种疫苗后的后续行动中，没有人经历过SARS-CoV-2感染。第一次注射BNT162b2后平均279.5天(SD5.5天)采集血清样本(图1A)。第一次接种BNT162b2后264.4天(SD5.8天)，平均抗RBD IgM为0.3C.O.(SD0.3)，这是基线水平，相当于第一次接种后第0天和第180天[4](图1B)。此外，在免疫后264.4天(图1C)，平均抗RBDIg G抗体为17.3AU/m L(SD13.1)，占第二次免疫后抗体的6.36%。在第三次接种后15天(279.5天)，抗-SARS-CoV-2IgM略有升高，但显著升高(平均1.7C.O.I.[SD3.9]，增加5.7倍)(图1B)，而抗SARS-CoV-2免疫球蛋白增加更明显(平均，702.9 AU/mL[SD402.9]，增加40.6倍)(图1C)。最近，发表了在60岁以上成年人(n=97)接种第三剂SARS-CoV-2BNT162b2疫苗前后的抗体滴度[7]。在他们的研究中，抗体效价的中位数从440增加到25,468(AU/毫升)，没有重大的不良反应。来自回溯性队列研究，Sacuk等人。[9]得出的结论是，对于6个月前接种疫苗的人来说，第三剂疫苗对SARS-CoV-2感染具有额外的保护作用。Barda等人。[10]最近，他利用以色列一半以上人口的强制性保健覆盖范围的数据证明了这一点，并将72.8万接受第三剂疫苗接种的个人与没有接种第三剂疫苗的人口统计学和临床上相似的对照组进行了比较。结果，在接种三剂疫苗的人群中，入院人数(231人比29人)、严重疾病(157人比17人)和死亡率(44人比7人)显著减少[10]。接种BNT162b2疫苗的长期疗效有待确定。我们目前的研究可能存在局限性，如样本量小，缺乏细胞免疫测试和中和抗体测试。然而，基于我们对免疫球蛋白急剧增加的观察*通讯作者：东北医科大学药科大学实验室医学部Shinichiro Takahashi，1-15-1，Fukumuro，Miyagino-ku，仙台，983-8536，Japan，电话：+81 22 290 8889，电子邮件：shintakahashi@Tohoku-mpu.ac.jp Rikei Kozakai，Kuniko Hoshi和Yoshihiko Izumi，日本仙台东北医科大学医院临床实验室，J Lab Med 2022；46(2)：151-153
As of the end of January 2022, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 351 million individuals worldwide and caused more than 5.6 million deaths. In the year of 2021, numerous groups, including us, have been reported about humoral responses and side effects after two doses of BNT162b2 vaccinations [1–4]. Subsequently, third dose of SARS-CoV-2 vaccination have just started from December 1, 2021 in Japan. Currently, several groups have started to report humoral responses after third doses of vaccinations, indicating an efficacy of a third dose [5–7]. However, further studies are warranted to verify these findings. Our group have recently reported antibody titers and side effects after two doses of BNT162b2 vaccination [4], and subsequent study of antibody decline 6 months after first vaccination [8]. In the current study, we examined levels of SARS-CoV-2 antibodies among healthy volunteers at Tohoku Medical and Pharmaceutical University Hospital, before and after vaccination with the Pfizer/BioNTechBNT162b2mRNAvaccine for the third time. Antibody titers were evaluated using a newly established, highly sensitive, fully automated chemiluminescent enzyme immunoassay (CLEIA) designed to specifically detect IgG and IgM against the SARS-CoV-2 spike protein receptor-binding domain (RBD) as described [4, 8]. Of 41 volunteers who received two doses of BNT162b2 at our hospital, all completed 9 months of follow-up after the first dose. At the time of writing, all 41 participants have completed this period, and none experienced SARS-CoV-2 infections prior to third vaccination or during post-third vaccination follow-up. Serum samples were obtained on average 279.5 days (SD 5.5 days) after the first dose of BNT162b2 (Figure 1A). 264.4 days (SD 5.8 days) after the first dose of BNT162b2, mean anti-RBD IgM was 0.3 C.O.I. (SD 0.3), which was baseline level and equal to day 0 and 180 days after first vaccination [4] (Figure 1B). Additionally, mean anti-RBD IgG antibodies was 17.3 AU/mL (SD 13.1) at 264.4 days after vaccination (Figure 1C),whichwas 6.36%of the antibody after the second dose. At 15 days after the third vaccination (day 279.5), anti-SARS-CoV-2 IgM was modestly but significantly increased (average, 1.7 C.O.I. [SD 3.9], 5.7-fold increase) (Figure 1B), while anti-SARS-CoV-2 IgG was more markedly increased (average, 702.9 AU/mL [SD 402.9], 40.6-fold increase) (Figure 1C). Quite recently, the antibody titers before and after a third dose of the SARS-Cov-2 BNT162b2 vaccine in adults agedmore that 60 years (n=97) have been published [7]. In their study, median IgG titer was increased from 440 to 25,468 (AU/mL), with no major adverse events. From the retrospective cohort study, Saciuk et al. [9], concluded that the third dose provides added protection against SARS-CoV-2 infection for those vaccinated 6 months ago. Barda et al. [10], recently demonstrated that using data from mandatory health-care coverage for over half of the Israeli population, and compared 0.728 million individuals receiving a third vaccine dose to demographically and clinically similar controls who did not receive a third dose. As a result, admission to hospital (231 vs. 29), severe disease (157 vs. 17) and death (44 vs. 7) is significantly reduced in the population vaccinated with three doses [10]. The long-term efficacy of BNT162b2 vaccination remains to be determined. Our current study may have limitations, such as small sample size, lack of cellular immunity testing and neutralizing antibody testing. However, based on our observations of dramatic increase of IgG *Corresponding author: Shinichiro Takahashi, Division of Laboratory Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1, Fukumuro, Miyagino-ku, Sendai, 983-8536, Japan, Phone: +81 22 290 8889, E-mail: shintakahashi@tohoku-mpu.ac.jp Rikei Kozakai, Kuniko Hoshi and Yoshihiko Izumi, Department of Clinical Laboratory, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Japan J Lab Med 2022; 46(2): 151–153