As COVID-19 continues to spread rapidly worldwide and variants continue to emerge, the development and deployment of safe and effective vaccines are urgently needed. Here, we developed an mRNA vaccine based on the trimeric receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein fused to ferritin-formed nanoparticles (TF-RBD). Compared to the trimeric form of the RBD mRNA vaccine (T-RBD), TF-RBD delivered intramuscularly elicited robust and durable humoral immunity as well as a Th1-biased cellular response. After further challenge with live SARS-CoV-2, immunization with a two-shot low-dose regimen of TF-RBD provided adequate protection in hACE2-transduced mice. In addition, the mRNA template of TF-RBD was easily and quickly engineered into a variant vaccine to address SARS-CoV-2 mutations. The TF-RBD multivalent vaccine produced broad-spectrum neutralizing antibodies against Alpha (B.1.1.7) and Beta (B.1.351) variants. This mRNA vaccine based on the encoded self-assembled nanoparticle-based trimer RBD provides a reference for the design of mRNA vaccines targeting SARS-CoV-2.
【저자키워드】 Infectious diseases, Vaccines, 【초록키워드】 COVID-19, neutralizing antibody, SARS-CoV-2, Vaccine, mRNA vaccine, B.1.351, variant, ferritin, immunization, variants, hACE2, mRNA vaccines, Spread, Protein, Humoral immunity, B.1.1.7, mice, RBD, mRNA, low-dose, Alpha, Beta, SARS-CoV-2 mutations, multivalent vaccine, SARS-CoV-2 spike, cellular response, Safe, regimen, domain, live SARS-CoV-2, trimer, trimeric, robust, produced, addition, provided, provide, the RBD, effective vaccine, elicited, fused, intramuscularly, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2, protective immunity, mice, trimeric RBD, robust, elicit,