National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China.
Front Immunol. 2023 Jan 5;13:1051576. doi: 10.3389/fimmu.2022.1051576. eCollection 2022.
The development of vaccines that can efficiently prevent the infection of SARS-CoV-2 is necessary to fight the COVID-19 epidemic. mRNA vaccine has been proven to induce strong humoral and cellular immunity against SARS-CoV-2. Here, we studied the immunogenicity and protection efficacy of a novel mRNA vaccine SYS6006. High expression of mRNA molecules in 293T cells was detected. The initial and boost immunization with a 21-day interval was determined as an optimal strategy for SYS6006. Two rounds of immunization with SYS6006 were able to induce the neutralizing antibodies against the SARS-CoV-2 wild-type (WT) strain, and Delta and Omicron BA.2 variants in mice or non-human primates (NHPs). A3 round of vaccination could further enhance the titers of neutralization against Delta and Omicron variants. ELISpot assay showed that SYS6006 could induce memory B cell and T cell immunities specifically against SARS-CoV-2 in mice. FACS analysis indicated that SYS6006 successfully induced SARS-CoV-2-specific activation of T follicular helper cell (Tfh) and Th1 cell, and did not induce CD4Th2 response in NHPs. SYS6006 vaccine could significantly reduce the viral RNA loads and prevent lung lesions in Delta variant infected hACE2 transgenic mice. Therefore, SYS6006 could provide significant immune protection against SARS-CoV-2.
开发能够有效预防 SARS-CoV-2 感染的疫苗对于抗击 COVID-19 疫情是必要的。mRNA 疫苗已被证明能诱导针对 SARS-CoV-2 的强烈体液和细胞免疫。在这里,我们研究了新型 mRNA 疫苗 SYS6006 的免疫原性和保护效力。在 293T 细胞中检测到高表达的 mRNA 分子。确定以 21 天间隔进行初始和加强免疫是 SYS6006 的最佳策略。两轮 SYS6006 免疫能够诱导小鼠或非人类灵长类动物(NHP)针对 SARS-CoV-2 野生型(WT)株、Delta 和 Omicron BA.2 变异株的中和抗体。第三轮接种可进一步提高针对 Delta 和 Omicron 变异株的中和抗体滴度。ELISpot 分析表明,SYS6006 能够在小鼠中特异性诱导针对 SARS-CoV-2 的记忆 B 细胞和 T 细胞免疫。FACS 分析表明,SYS6006 成功诱导了 SARS-CoV-2 特异性滤泡辅助性 T 细胞(Tfh)和 Th1 细胞的激活,而在 NHP 中没有诱导 CD4Th2 反应。SYS6006 疫苗可显著降低 Delta 变异株感染 hACE2 转基因小鼠的病毒 RNA 载量并预防肺部病变。因此,SYS6006 可以为 SARS-CoV-2 提供显著的免疫保护。