Abstract：
The spread of SARS-CoV-2 and its variants leads to a heavy burden on healthcare and the global economy, highlighting the need for developing vaccines that induce broad immunity against coronavirus. Here, we explored the immunogenicity of monovalent or bivalent spike (S) trimer subunit vaccines derived from SARS-CoV-2 B.1.351 (S1-2P) or/and B.1. 618 (S2-2P) in Balb/c mice. Both S1-2P and S2-2P elicited anti-spike antibody responses, and alum adjuvant induced higher levels of antibodies than Addavax adjuvant. The dose responses of the vaccines on immunogenicity were evaluated in vivo. A low dose of 5 μg monovalent recombinant protein or 2.5 μg bivalent vaccine triggered high-titer antibodies that showed cross-activity to Beta, Delta, and Gamma RBD in mice. The third immunization dose could boost (1.1 to 40.6 times) high levels of cross-binding antibodies and elicit high titers of neutralizing antibodies (64 to 1024) prototype, Beta, Delta, and Omicron variants. Furthermore, the vaccines were able to provoke a Th1-biased cellular immune response. Significantly, at the same antigen dose, S1-2P immune sera induced stronger broadly neutralizing antibodies against prototype, Beta, Delta, and Omicron variants compared to that induced by S2-2P. At the same time, the low dose of bivalent vaccine containing S2-2P and S1-2P (2.5 μg for each antigen) significantly improved the cross-neutralizing antibody responses. In conclusion, our results showed that monovalent S1-2P subunit vaccine or bivalent vaccine (S1-2P and S2-2P) induced potent humoral and cellular responses against multiple SARS-CoV-2 variants and provided valuable information for the development of recombinant protein-based SARS-CoV-2 vaccines that protect against emerging SARS-CoV-2 variants.
摘要：
SARS-CoV-2及其变体的传播给医疗保健和全球经济带来了沉重的负担，强调需要开发诱导针对冠状病毒的广泛免疫力的疫苗。这里,我们探索了源自SARS-CoV-2B.1.351（S1-2P）或/和B.1.的单价或二价刺突（S）三聚体亚单位疫苗的免疫原性。618(S2-2P)在Balb/c小鼠中。S1-2P和S2-2P均引发抗尖峰抗体反应，和明矾佐剂比Addavax佐剂诱导更高水平的抗体。在体内评估疫苗对免疫原性的剂量反应。低剂量的5μg单价重组蛋白或2.5μg二价疫苗触发高滴度抗体，显示出与Beta，Delta,和小鼠的GammaRBD。第三次免疫剂量可以增强（1.1至40.6倍）高水平的交叉结合抗体，并引发高滴度的中和抗体（64至1024）原型，Beta,Delta,和Omicron变体。此外，这些疫苗能够激发Th1偏倚的细胞免疫应答.重要的是,在相同的抗原剂量下，S1-2P免疫血清诱导针对原型的更强的广泛中和抗体，Beta,Delta,和Omicron变体与S2-2P诱导的变体相比。同时,低剂量的含有S2-2P和S1-2P的二价疫苗(每种抗原2.5μg)显著改善了交叉中和抗体应答.总之,我们的结果表明,单价S1-2P亚单位疫苗或二价疫苗(S1-2P和S2-2P)诱导了针对多种SARS-CoV-2变体的强效体液和细胞应答,并为开发基于重组蛋白的SARS-CoV-2疫苗提供了有价值的信息,该疫苗可预防新出现的SARS-CoV-2变体.
