Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity  

作　　者：Fuhua Wu Shuang Luo Yongshun Zhang Yangsen Ou Hairui Wang Zhaofei Guo Chunting He Shuting Bai Penghui He Min Jiang Xiaoyan Chen Guangsheng Du Xun Sun 

机构地区：[1]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province,Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology,West China School of Pharmacy,Sichuan University,Chengdu 610041,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第5期2219-2233,共15页药学学报（英文版）

基　　金：the National Natural Science Foundation of China,China(Grant Nos.81925036 and 81872814);the Key Research and Development Program of Science and Technology Department of Sichuan Province,China(Grant No.2020YFS0570);111 project,China(Grant No.B18035);the Fundamental Research Funds for the Central Universities,China。

摘　　要：Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines,the epidemic prevention and control are still challenging.Here,we employ a capsid and antigen structure engineering(CASE)strategy to manufacture an adenoassociated viral serotype 6-based vaccine(S663V-RBD),which expresses trimeric receptor binding domain(RBD)of spike protein fused with a biological adjuvant RS09.Impressively,the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months.Compared to the licensed BBIBP-CorV(Sinopharm,China),a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type,C.37(Lambda)and B.1.617.2(Delta).More interestingly,the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid.Given its effectiveness,the CASE-based S663VRBD may provide a new solution for the current and next pandemic.

关 键 词：AAV vectors Capsid engineering VACCINE Antigen structure design SARS-CoV-2 

分 类 号：R392-33[医药卫生—免疫学]