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 adeno-associated 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 su-perior 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 S663V-RBD may provide a new solution for the current and next pandemic.