Wang Rui, Sun Chunyun, Ma Juan, Yu Chulin, Kong Desheng, Chen Meng, Liu Xuejie, Zhao Dandan, Gao Shuman, Kou Shuyuan, Sun Lili, Ge Zeyong, Zhao Jun, Li Kuokuo, Zhang Tao, Zhang Yanjing, Luo Chunxia, Li Xuefeng, Wang Yang, Xie Liangzhi
Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, China.
Cell Culture Engineering Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100176, China.
Vaccines (Basel). 2022 Apr 29;10(5):702. doi: 10.3390/vaccines10050702.
With the emergence and rapid spread of new pandemic variants, especially variants of concern (VOCs), the development of next-generation vaccines with broad-spectrum neutralizing activities is of great importance. In this study, SCTV01C, a clinical stage bivalent vaccine based on trimeric spike extracellular domain (S-ECD) of SARS-CoV-2 variants Alpha (B.1.1.7) and Beta (B.1.351) with a squalene-based oil-in-water adjuvant was evaluated in comparison to its two corresponding (Alpha and Beta) monovalent vaccines in mouse immunogenicity studies. The two monovalent vaccines induced potent neutralizing antibody responses against the antigen-matched variants, but drastic reductions in neutralizing antibody titers against antigen-mismatched variants were observed. In comparison, the bivalent vaccine SCTV01C induced relatively higher and broad-spectrum cross-neutralizing activities against various SARS-CoV-2 variants, including the D614G variant, VOCs (B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.1.529), variants of interest (VOIs) (C.37, B.1.621), variants under monitoring (VUMs) (B.1.526, B.1.617.1, B.1.429, C.36.3) and other variants (B.1.618, 20I/484Q). All three vaccines elicited potent Th1-biased T-cell immune responses. These results provide direct evidence that variant-based multivalent vaccines could play important roles in addressing the critical issue of reduced protective efficacy against the existing and emerging SARS-CoV-2 variants.
随着新型大流行变异株，尤其是值得关注的变异株（VOCs）的出现和迅速传播，开发具有广谱中和活性的下一代疫苗至关重要。在本研究中，在小鼠免疫原性研究中，将SCTV01C（一种基于严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变异株阿尔法（B.1.1.7）和贝塔（B.1.351）三聚体刺突细胞外结构域（S-ECD）的临床阶段二价疫苗，佐以基于角鲨烯的水包油佐剂）与其两种相应的（阿尔法和贝塔）单价疫苗进行了比较评估。两种单价疫苗诱导了针对抗原匹配变异株的强效中和抗体反应，但观察到针对抗原不匹配变异株的中和抗体滴度大幅降低。相比之下，二价疫苗SCTV01C诱导了针对各种SARS-CoV-2变异株的相对较高的广谱交叉中和活性，包括D614G变异株、VOCs（B.1.1.7、B.1.351、P.1、B.1.617.2、B.1.1.529）、感兴趣的变异株（VOIs）（C.37、B.1.621）、监测中的变异株（VUMs）（B.1.526、B.1.617.1、B.1.429、C.36.3）和其他变异株（B.1.618、20I/484Q）。所有三种疫苗都引发了强效的以Th1为主的T细胞免疫反应。这些结果提供了直接证据，表明基于变异株的多价疫苗在解决针对现有和新出现的SARS-CoV-2变异株保护效力降低这一关键问题方面可发挥重要作用。
