United Biomedical (UBI), Inc., Hauppauge, New York, USA.
UBI Asia, Hsinchu, Taiwan.
J Clin Invest. 2022 May 16;132(10). doi: 10.1172/JCI157707.
BackgroundThe Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.MethodWe conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 μg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 μg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 μg of UB-612 (n = 3,875, 18-85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.ResultsNo vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.ConclusionUB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.Trial RegistrationClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.FundingUBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.
背景
SARS-CoV-2 的德尔塔和奥密克戎变体目前由于免疫减弱而导致突破性感染。我们报告了 UB-612 的 I/II 期试验结果，UB-612 是一种包含 S1-RBD-sFc 蛋白和合理设计的混杂肽的多表位亚单位疫苗，这些混杂肽代表核衣壳 (N)、膜 (M) 和刺突 (S2) 蛋白上的沙贝科病毒保守辅助 T 细胞和细胞毒性 T 淋巴细胞表位。
方法
我们在 60 名 20 至 55 岁的健康年轻成年人中进行了一项 I 期的两剂（间隔 28 天）试验，分别使用 10、30 或 100 μg 的 UB-612，其中 50 名在第二剂后大约 7 至 9 个月接受了 100 μg 的 UB-612 加强针。一项单独的安慰剂对照和随机的 II 期研究使用了两剂 100 μg 的 UB-612（n = 3,875，18-85 岁）。我们评估了 I 期直至第 3 剂（加强剂）后 14 天和 II 期直至第 2 剂后 28 天的临时安全性和免疫原性。
结果
没有与疫苗相关的严重不良事件记录。最常见的不良事件是注射部位疼痛和疲劳，大多为轻度和短暂性的。在两项试验中，UB-612 分别诱导了与一组人类恢复期血清相似的中和抗体滴度。最引人注目的发现是针对 SARS-CoV-2 关注变体（VoCs）的持久病毒中和抗体和广泛的 T 细胞免疫，包括德尔塔和奥密克戎，以及强烈的加强剂回忆记忆免疫，对德尔塔和奥密克戎 VoCs 具有高交叉反应性中和滴度。
结论
UB-612 表现出良好的安全性，对 VoCs 具有强大的加强作用，以及持久的 B 细胞和广泛的 T 细胞免疫，这为其在初级免疫和其他 COVID-19 疫苗的异源加强方面的进一步发展提供了依据。
试验注册
ClinicalTrials.gov：NCT04545749、NCT04773067 和 NCT04967742。
资金
UBI Asia、Vaxxinity Inc. 和台湾疾病管制署、卫生福利部。
