School of Public Health, Department of Epidemiology, Iran University of Medical Science, Tehran, Iran.
Department of Immunology, Agricultural Research, Education and Extension Organization (AREEO), Razi Vaccine and Serum Research Institute, Karaj, Iran.
BMC Med. 2024 Feb 20;22(1):78. doi: 10.1186/s12916-024-03295-1.
The immunity induced by primary vaccination is effective against COVID-19; however, booster vaccines are needed to maintain vaccine-induced immunity and improve protection against emerging variants. Heterologous boosting is believed to result in more robust immune responses. This study investigated the safety and immunogenicity of the Razi Cov Pars vaccine (RCP) as a heterologous booster dose in people primed with Beijing Bio-Institute of Biological Products Coronavirus Vaccine (BBIBP-CorV).
We conducted a randomized, double-blind, active-controlled trial in adults aged 18 and over primarily vaccinated with BBIBP-CorV, an inactivated SARS-CoV-2 vaccine. Eligible participants were randomly assigned (1:1) to receive a booster dose of RCP or BBIBP-CorV vaccines. The primary outcome was neutralizing antibody activity measured by a conventional virus neutralization test (cVNT). The secondary efficacy outcomes included specific IgG antibodies against SARS-CoV-2 spike (S1 and receptor-binding domain, RBD) antigens and cell-mediated immunity. We measured humoral antibody responses at 2 weeks (in all participants) and 3 and 6 months (a subgroup of 101 participants) after the booster dose injection. The secondary safety outcomes were solicited and unsolicited immediate, local, and systemic adverse reactions.
We recruited 483 eligible participants between December 7, 2021, and January 13, 2022. The mean age was 51.9 years, and 68.1% were men. Neutralizing antibody titers increased about 3 (geometric mean fold increase, GMFI = 2.77, 95% CI 2.26-3.39) and 21 (GMFI = 21.51, 95% CI 16.35-28.32) times compared to the baseline in the BBIBP-CorV and the RCP vaccine groups. Geometric mean ratios (GMR) and 95% CI for serum neutralizing antibody titers for RCP compared with BBIBP-CorV on days 14, 90, and 180 were 6.81 (5.32-8.72), 1.77 (1.15-2.72), and 2.37 (1.62-3.47) respectively. We observed a similar pattern for specific antibody responses against S1 and RBD. We detected a rise in gamma interferon (IFN-γ), tumor necrosis factor (TNF-α), and interleukin 2 (IL-2) following stimulation with S antigen, particularly in the RCP group, and the flow cytometry examination showed an increase in the percentage of CD3 + /CD8 + lymphocytes. RCP and BBIBP-CorV had similar safety profiles; we identified no vaccine-related or unrelated deaths.
BBIBP-CorV and RCP vaccines as booster doses are safe and provide a strong immune response that is more robust when the RCP vaccine is used. Heterologous vaccines are preferred as booster doses.
This study was registered with the Iranian Registry of Clinical Trial at www.irct.ir , IRCT20201214049709N4. Registered 29 November 2021.
初级疫苗接种诱导的免疫可有效预防 COVID-19；然而，需要加强针来维持疫苗诱导的免疫并提高对新兴变异株的保护。异源加强针被认为会产生更强大的免疫反应。本研究旨在评估 Razi Cov Pars 疫苗（RCP）作为异源加强针在已接种北京生物制品研究所冠状病毒疫苗（BBIBP-CorV）的人群中的安全性和免疫原性。
我们在成年人中开展了一项随机、双盲、阳性对照的临床试验，这些成年人已接种过 BBIBP-CorV（一种灭活的 SARS-CoV-2 疫苗）作为初级疫苗。符合条件的参与者被随机分配（1:1）接受 RCP 或 BBIBP-CorV 疫苗的加强针。主要结局是通过传统病毒中和试验（cVNT）测量的中和抗体活性。次要疗效结局包括针对 SARS-CoV-2 刺突（S1 和受体结合域，RBD）抗原的特异性 IgG 抗体和细胞介导免疫。我们在加强针注射后 2 周（所有参与者）和 3 个月和 6 个月（101 名参与者的亚组）测量了体液抗体反应。次要安全性结局为主动和被动报告的即刻、局部和全身不良事件。
我们于 2021 年 12 月 7 日至 2022 年 1 月 13 日期间招募了 483 名符合条件的参与者。参与者的平均年龄为 51.9 岁，68.1%为男性。与基线相比，BBIBP-CorV 和 RCP 组的中和抗体滴度分别增加了约 3（几何平均倍数增加，GMFI=2.77，95%CI 2.26-3.39）和 21（GMFI=21.51，95%CI 16.35-28.32）倍。RCP 与 BBIBP-CorV 相比，在第 14、90 和 180 天血清中和抗体滴度的几何均数比（GMR）和 95%CI 分别为 6.81（5.32-8.72）、1.77（1.15-2.72）和 2.37（1.62-3.47）。我们观察到针对 S1 和 RBD 的特异性抗体反应也存在类似的模式。我们在刺激 S 抗原后检测到了 IFN-γ、TNF-α 和 IL-2 的上升，尤其是在 RCP 组中，流式细胞术检查显示 CD3+/CD8+淋巴细胞的百分比增加。RCP 和 BBIBP-CorV 具有相似的安全性特征；我们未发现与疫苗相关或不相关的死亡。
BBIBP-CorV 和 RCP 疫苗作为加强针是安全的，并能产生强烈的免疫反应，而 RCP 疫苗产生的免疫反应更强。异源疫苗作为加强针更受欢迎。
本研究在伊朗临床试验注册中心 www.irct.ir 进行注册，注册号为 IRCT20201214049709N4。注册日期为 2021 年 11 月 29 日。
