抗 SARS-CoV-2 疫苗 SOBERANA 02 同源或异源方案的安全性和免疫原性：开放标签 I 期和 IIa 期临床试验。
Safety and immunogenicity of anti-SARS CoV-2 vaccine SOBERANA 02 in homologous or heterologous scheme: Open label phase I and phase IIa clinical trials.
机构信息
"Pedro Kourí" Tropical Medicine Institute, Av "Novia del Mediodía", Kv 6 1/2, La Lisa, Habana 11400, Cuba.
Clinic #1. 21 St. and 190, La Lisa, Habana, Cuba.
出版信息
Vaccine. 2022 Jul 29;40(31):4220-4230. doi: 10.1016/j.vaccine.2022.05.082. Epub 2022 Jun 6.
BACKGROUND
SOBERANA 02 is a COVID-19 vaccine based on SARS-CoV-2 recombinant RBD conjugated to tetanus toxoid (TT). SOBERANA Plus antigen is dimeric-RBD. Here we report safety and immunogenicity from phase I and IIa clinical trials using two-doses of SOBERANA 02 and three-doses (homologous) or heterologous (with SOBERANA Plus) protocols.
METHOD
We performed an open-label, sequential and adaptive phase I to evaluate safety and explore the immunogenicity of SOBERANA 02 in two formulations (15 or 25 μg RBD-conjugated to 20 μg of TT) in 40 subjects, 19-59-years-old. Phase IIa was open-label including 100 volunteers 19-80-years, receiving two doses of SOBERANA 02-25 μg. In both trials, half of volunteers were selected to receive a third dose of the corresponding SOBERANA 02 and half received a heterologous dose of SOBERANA Plus. Primary outcome was safety. The secondary outcome was immunogenicity evaluated by anti-RBD IgG ELISA, molecular neutralization of RBD:hACE2 interaction, live-virus-neutralization and specific T-cells response.
RESULTS
The most frequent adverse event (AE) was local pain, other AEs had frequencies ≤ 5%. No serious related-AEs were reported. Phase IIa confirmed the safety in 60 to 80-years-old subjects. In phase-I SOBERANA 02-25 µg elicited higher immune response than SOBERANA 02-15 µg and progressed to phase IIa. Phase IIa results confirmed the immunogenicity of SOBERANA 02-25 µg even in 60-80-years. Two doses of SOBERANA02-25 µg elicited an immune response similar to that of the Cuban Convalescent Serum Panel and it was higher after the homologous and heterologous third doses. The heterologous scheme showed a higher immunological response. Anti-RBD IgG neutralized the delta variant in molecular assay, with a 2.5-fold reduction compared to D614G neutralization.
CONCLUSIONS
SOBERANA 02 was safe and immunogenic in persons aged 19-80 years, eliciting neutralizing antibodies and specific T-cell response. Highest immune responses were obtained in the heterologous three doses protocol.
TRIAL REGISTRY
https://rpcec.sld.cu/trials/RPCEC00000340, https://rpcec.sld.cu/trials/RPCEC00000347.
背景
SOBERANA 02 是一种基于 SARS-CoV-2 重组 RBD 与破伤风类毒素（TT）结合的 COVID-19 疫苗。SOBERANA Plus 抗原是二聚体-RBD。在这里，我们报告了使用两种剂量的 SOBERANA 02 和三种剂量（同源）或异源（与 SOBERANA Plus）方案进行的 I 期和 IIa 临床试验的安全性和免疫原性。
方法
我们进行了一项开放性、序贯和适应性 I 期研究，以评估安全性并在 40 名 19-59 岁的受试者中使用两种制剂（15 或 25μg RBD 与 20μg TT 结合）探索 SOBERANA 02 的免疫原性。IIa 期为开放性，包括 100 名 19-80 岁的志愿者，接受两剂 SOBERANA 02-25μg。在这两项试验中，一半的志愿者被选择接受第三剂相应的 SOBERANA 02，另一半接受 SOBERANA Plus 的异源剂量。主要结局是安全性。次要结局是通过抗-RBD IgG ELISA、RBD:hACE2 相互作用的分子中和、活病毒中和和特异性 T 细胞反应评估免疫原性。
结果
最常见的不良事件（AE）是局部疼痛，其他 AE 的频率≤5%。没有报告与治疗相关的严重不良事件。IIa 期在 60-80 岁的受试者中确认了安全性。在 I 期，SOBERANA 02-25μg 比 SOBERANA 02-15μg 产生更高的免疫反应，并进展到 IIa 期。IIa 期结果证实，即使在 60-80 岁的人群中，SOBERANA 02-25μg 也具有免疫原性。两剂 SOBERANA02-25μg 产生的免疫反应与古巴恢复期血清组相当，同源和异源第三剂后更高。异源方案显示出更高的免疫反应。抗-RBD IgG 在分子检测中中和了 delta 变异体，与 D614G 中和相比，降低了 2.5 倍。
结论
SOBERANA 02 在 19-80 岁人群中安全且具有免疫原性，可诱导中和抗体和特异性 T 细胞反应。异源三剂量方案可获得最高的免疫反应。
试验注册
https://rpcec.sld.cu/trials/RPCEC00000340，https://rpcec.sld.cu/trials/RPCEC00000347。
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