Evolution of SARS-CoV-2 variants emphasizes the need for multivalent vaccines capable of simultaneously targeting multiple strains. SCTV01E is a tetravalent COVID-19 vaccine derived from the spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1. In this double-blinded placebo-controlled pivotal efficacy trial (NCT05308576), the primary endpoint was vaccine efficacy (VE) against COVID-19 seven days post-vaccination in individuals without recent infection. Other endpoints included evaluating safety, immunogenicity, and the VE against all SARS-CoV-2 infections in individuals meeting the study criteria. Between December 26, 2022, and January 15, 2023, 9,223 individuals were randomized at a 1:1 ratio to receive SCTV01E or a placebo. SCTV01E showed a VE of 69.4% (95% CI: 50.6, 81.0) 7 days post-vaccination, with 75 cases in the placebo group and 23 in the SCTV01E group for the primary endpoint. VEs were 79.7% (95% CI: 51.0, 91.6) and 82.4% (95% CI: 57.9, 92.6), respectively, for preventing symptomatic infection and all SARS-CoV-2 infections 14 days post-vaccination. SCTV01E elicited a 25.0-fold higher neutralizing antibody response against Omicron BA.5 28 days post-vaccination compared to placebo. Reactogenicity was generally mild and transient, with no reported vaccine-related SAE, adverse events of special interest (AESI), or deaths. The trial aligned with the shift from dominant variants BA.5 and BF.7 to XBB, suggesting SCTV01E as a potential vaccine alternative effective against present and future variants.

SARS-CoV-2 变体的进化强调需要能够同时针对多种毒株的多价疫苗。 SCTV01E 是一种四价 COVID-19 疫苗，源自 SARS-CoV-2 变种 Alpha、Beta、Delta 和 Omicron BA.1 的刺突蛋白。在这项双盲安慰剂对照关键疗效试验 (NCT05308576) 中，主要终点是近期未感染的个体在接种疫苗 7 天后针对 COVID-19 的疫苗功效 (VE)。其他终点包括评估符合研究标准的个体对所有 SARS-CoV-2 感染的安全性、免疫原性和 VE。 2022年12月26日至2023年1月15日期间，9,223名受试者以1:1的比例随机接受SCTV01E或安慰剂治疗。 SCTV01E 在疫苗接种后 7 天显示 VE 为 69.4%（95% CI：50.6，81.0），主要终点为安慰剂组 75 例，SCTV01E 组 23 例。接种后 14 天预防症状感染和所有 SARS-CoV-2 感染的 VE 分别为 79.7%（95% CI：51.0、91.6）和 82.4%（95% CI：57.9、92.6）。与安慰剂相比，SCTV01E 在疫苗接种后 28 天引发的针对 Omicron BA.5 的中和抗体反应高出 25.0 倍。反应原性通常是轻微且短暂的，没有报告与疫苗相关的 SAE、特别关注的不良事件 (AESI) 或死亡。该试验与显性变体 BA.5 和 BF.7 向 XBB 的转变相一致，表明 SCTV01E 作为有效对抗当前和未来变体的潜在疫苗替代品。