National Centre of Toxicology (CENATOX), 31 Ave. and 114 Street, Marianao, Havana, Cuba.
Finlay Vaccine Institute. 21(st) Ave. N° 19810 between 198 and 200 Streets, Atabey, Playa, Havana, Cuba.
Vaccine. 2022 Mar 18;40(13):2068-2075. doi: 10.1016/j.vaccine.2022.02.029. Epub 2022 Feb 8.
The Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is the target for many COVID-19 vaccines. Here we report results for phase I clinical trial of two COVID-19 vaccine candidates based on recombinant dimeric RBD (d-RBD).
We performed a randomized, double-blind, phase I clinical trial in the National Centre of Toxicology in Havana. Sixty Cuban volunteers aged 19-59 years were randomized into three groups (20 subjects each): 1) FINLAY-FR-1 (50 µg d-RBD plus outer membrane vesicles from N. meningitidis); 2) FINLAY-FR-1A-50 (50 µg d-RBD, three doses); 3) FINLAY-FR-1A-25 (25 µg d-RDB, three doses). The FINLAY-FR-1 group was randomly divided to receive a third dose of the same vaccine candidate (homologous schedule) or FINLAY-FR-1A-50 (heterologous schedule). The primary outcomes were safety and reactogenicity. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following each vaccination was evaluated using live-virus neutralization test, anti-RBD IgG ELISA and in-vitro neutralization test of RBD:hACE2 interaction.
Most adverse events were of mild intensity (63.5%), solicited (58.8%), and local (61.8%); 69.4% with causal association with vaccination. Serious adverse events were not found. The FINLAY-FR-1 group reported more subjects with adverse events than the other two groups. After the third dose, anti-RBD seroconversion was 100%, 94.4% and 90% for the FINLAY-FR-1, FINLAY-FR-1A-50 and FINLAY-FR-1A-25 respectively. The in-vitro inhibition of RBD:hACE2 interaction increased after the second dose in all formulations. The geometric mean neutralizing titres after the third dose rose significantly in the group vaccinated with FINLAY-FR-1 with respect to the other formulations and the COVID-19 Convalescent Serum Panel. No differences were found between FINLAY-FR-1 homologous or heterologous schedules.
Vaccine candidates were safe and immunogenic, and induced live-virus neutralizing antibodies against SARS-CoV-2. The highest values were obtained when outer membrane vesicles were used as adjuvant.
SARS-CoV-2 刺突蛋白的受体结合域（RBD）是许多 COVID-19 疫苗的靶点。在此，我们报告了两种基于重组二聚体 RBD（d-RBD）的 COVID-19 候选疫苗的 I 期临床试验结果。
我们在哈瓦那国家毒理学中心进行了一项随机、双盲、I 期临床试验。60 名 19-59 岁的古巴志愿者被随机分为三组（每组 20 名）：1）FINLAY-FR-1（50μg d-RBD 加脑膜炎奈瑟菌外膜囊泡）；2）FINLAY-FR-1A-50（50μg d-RBD，三剂）；3）FINLAY-FR-1A-25（25μg d-RBD，三剂）。FINLAY-FR-1 组随机分为接受相同候选疫苗的第三剂（同源方案）或 FINLAY-FR-1A-50（异源方案）。主要结局是安全性和反应原性。次要结局是疫苗免疫原性。使用活病毒中和试验、抗 RBD IgG ELISA 和 RBD：hACE2 相互作用的体外中和试验评估基线和每次接种后的体液反应。
大多数不良事件为轻度（63.5%）、自限性（58.8%）和局部性（61.8%）；69.4%与疫苗接种有因果关系。未发现严重不良事件。与其他两组相比，FINLAY-FR-1 组报告的不良事件更多。第三剂后，FINLAY-FR-1、FINLAY-FR-1A-50 和 FINLAY-FR-1A-25 的抗 RBD 血清转化率分别为 100%、94.4%和 90%。所有配方的第二剂后，RBD：hACE2 相互作用的体外抑制均增加。与其他配方和 COVID-19 恢复期血清组相比，FINLAY-FR-1 组接种第三剂后，活病毒中和抗体滴度显著升高。在 FINLAY-FR-1 同源或异源方案之间未发现差异。
候选疫苗安全且具有免疫原性，可诱导针对 SARS-CoV-2 的活病毒中和抗体。当使用外膜囊泡作为佐剂时，获得了最高值。
