SOBERANA 02 和 SOBERANA Plus 疫苗异源方案的抗 SARS-CoV-2 安全性和免疫原性：成人 IIb 期临床试验。

Safety and immunogenicity of anti-SARS-CoV-2 heterologous scheme with SOBERANA 02 and SOBERANA Plus vaccines: Phase IIb clinical trial in adults.

机构信息

"Pedro Kourí" Tropical Medicine Institute, Av "Novia del Mediodía", Kv 6 1/2, La Lisa, Havana 11400, Cuba.

"19 de Abril" Polyclinic, Tulipan St. between Panorama y Oeste, Nuevo Vedado, Plaza de la Revolución, Havana 10400, Cuba.

出版信息

Med. 2022 Nov 11;3(11):760-773.e5. doi: 10.1016/j.medj.2022.08.001. Epub 2022 Aug 8.

BACKGROUND

SOBERANA 02 has been evaluated in phase I and IIa studies comparing homologous versus heterologous schedule (this one, including SOBERANA Plus). Here, we report results of immunogenicity, safety, and reactogenicity of SOBERANA 02 in a two- or three-dose heterologous scheme in adults.

METHOD

Phase IIb was a parallel, multicenter, adaptive, double-blind, randomized, and placebo-controlled trial. Subjects (n = 810) aged 19-80 years were randomized to receive two doses of SARS-CoV-2 RBD conjugated to tetanus toxoid (SOBERANA 02) and a third dose of dimeric RBD (SOBERANA Plus) 28 days apart; two production batches of active ingredients of SOBERANA 02 were evaluated. Primary outcome was the percentage of seroconverted subjects with ≥4-fold the anti-RBD immunoglobulin G (IgG) concentration. Secondary outcomes were safety, reactogenicity, and neutralizing antibodies.

FINDINGS

Seroconversion rate in vaccinees was 76.3% after two doses and 96.8% after the third dose of SOBERANA Plus (7.3% in the placebo group). Neutralizing IgG antibodies were detected against D614G and variants of concern (VOCs) Alpha, Beta, Delta, and Omicron. Specific, functional antibodies were detected 7-8 months after the third dose. The frequency of serious adverse events (AEs) associated with vaccination was very low (0.1%). Local pain was the most frequent AE.

CONCLUSIONS

Two doses of SOBERANA 02 were safe and immunogenic in adults. The heterologous combination with SOBERANA Plus increased neutralizing antibodies, detectable 7-8 months after the third dose.

TRIAL REGISTRY

https://rpcec.sld.cu/trials/RPCEC00000347 FUNDING: This work was supported by Finlay Vaccine Institute, BioCubaFarma, and the Fondo Nacional de Ciencia y Técnica (FONCI-CITMA-Cuba, contract 2020-20).

背景

SOBERANA 02 已在 I 期和 IIa 期研究中进行了评估，比较了同源和异源方案（包括本研究中的 SOBERANA Plus）。在此，我们报告了在成人中采用两剂或三剂异源方案时 SOBERANA 02 的免疫原性、安全性和反应原性结果。

方法

IIb 期为平行、多中心、适应性、双盲、随机、安慰剂对照试验。年龄在 19-80 岁的受试者（n=810）被随机分为两组，分别在 28 天内接受两剂 SARS-CoV-2 RBD 与破伤风类毒素结合的疫苗（SOBERANA 02）和第三剂二聚体 RBD（SOBERANA Plus）；评估了 SOBERANA 02 的两种活性成分生产批次。主要结局是抗-RBD 免疫球蛋白 G（IgG）浓度≥4 倍升高的血清转化受试者的百分比。次要结局是安全性、反应原性和中和抗体。

发现

两剂 SOBERANA 02 后疫苗接种者的血清转化率为 76.3%，第三剂 SOBERANA Plus 后为 96.8%（安慰剂组为 7.3%）。针对 D614G 和关注变体（VOC）Alpha、Beta、Delta 和 Omicron 检测到中和 IgG 抗体。第三剂后 7-8 个月可检测到特异性、功能性抗体。与疫苗接种相关的严重不良事件（AE）的频率非常低（0.1%）。局部疼痛是最常见的 AE。