A spike-trimer protein-based tetravalent COVID-19 vaccine elicits enhanced breadth of neutralization against SARS-CoV-2 Omicron subvariants and other variants  

作　　者：Rui Wang Hongpeng Huang Chulin Yu Chunyun Sun Juan Ma Desheng Kong Yalong Lin Dandan Zhao Shaozheng Zhou Jianbo Lu Sai Cao Yanjing Zhang Chunxia Luo Xuefeng Li Yang Wang Liangzhi Xie 

机构地区：[1]Beijing Protein and Antibody R&D Engineering Center,Sinocelltech Ltd.,Beijing 100176,China [2]Cell Culture Engineering Center,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100005,China

出　　处：《Science China(Life Sciences)》2023年第8期1818-1830,共13页中国科学（生命科学英文版）

基　　金：supported by Sinocelltech with grant support from Beijing Municipal Science and Technology Program(Z211100002521026,Z221100007922012)。

摘　　要：Multivalent vaccines combining crucial mutations from phylogenetically divergent variants could be an effective approach to defend against existing and future SARS-Co V-2 variants.In this study,we developed a tetravalent COVID-19 vaccine SCTV01E,based on the trimeric Spike protein of SARS-Co V-2 variants Alpha,Beta,Delta,and Omicron BA.1,with a squalenebased oil-in-water adjuvant SCT-VA02B.In the immunogenicity studies in na?ve BALB/c and C57BL/6J mice,SCTV01E exhibited the most favorable immunogenic characteristics to induce balanced and broad-spectrum neutralizing potencies against pre-Omicron variants(D614G,Alpha,Beta,and Delta)and newly emerging Omicron subvariants(BA.1,BA.1.1,BA.2,BA.3,and BA.4/5).Booster studies in C57BL/6J mice previously immunized with D614G monovalent vaccine demonstrated superior neutralizing capacities of SCTV01E against Omicron subvariants,compared with the D614G booster regimen.Furthermore,SCTV01E vaccination elicited na?ve and central memory T cell responses to SARS-Co V-2 ancestral strain and Omicron spike peptides.Together,our comprehensive immunogenicity evaluation results indicate that SCTV01E could become an important COVID-19 vaccine platform to combat surging infections caused by the highly immune evasive BA.4/5 variants.SCTV01E is currently being studied in a head-to-head immunogenicity comparison phase 3 clinical study with inactivated and m RNA vaccines(NCT05323461).

关 键 词：tetravalent SARS-CoV-2 vaccine Omicron subvariants broad neutralization 

分 类 号：R392-33[医药卫生—免疫学]