Qi Hailong, Sun Zhongjie, Yao Yanling, Chen Ligong, Su Xuncheng
State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
Hebei Immune Cell Application Engineering Research Center, Baoding Newish Technology Co., Ltd./Newish Technology (Beijing) Co., Ltd., Beijing 100176, China.
Vaccines (Basel). 2022 Mar 8;10(3):407. doi: 10.3390/vaccines10030407.
SARS-CoV-2 spike (S) variants that may evade antibody-mediated immunity are emerging. Evidence shows that vaccines with a stronger immune response are still effective against mutant strains. Here, we report a targeted type 1 conventional dendritic (cDC1) cell strategy for improved COVID-19 vaccine design. cDC1 cells specifically express X-C motif chemokine receptor 1 (Xcr1), the only receptor for chemokine Xcl1. We fused the gene sequence with the gene to deliver the expressed S protein to cDC1 cells. Immunization with a plasmid encoding the S protein fused to Xcl1 showed stronger induction of antibody and antigen-specific T cell immune responses than immunization with the plasmid alone in mice. The fusion gene-induced antibody also displayed more powerful SARS-CoV-2 wild-type virus and pseudovirus neutralizing activity. Xcl1 also increased long-lived antibody-secreting plasma cells in bone marrow. These preliminary results indicate that Xcl1 serves as a molecular adjuvant for the SARS-CoV-2 vaccine and that our Xcl1-S fusion DNA vaccine is a potential COVID-19 vaccine candidate for use in further translational studies.
可能逃避抗体介导免疫的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突（S）变体正在出现。有证据表明，具有更强免疫反应的疫苗对突变株仍然有效。在此，我们报告一种用于改进2019冠状病毒病（COVID-19）疫苗设计的靶向1型常规树突状（cDC1）细胞策略。cDC1细胞特异性表达X-C基序趋化因子受体1（Xcr1），即趋化因子Xcl1的唯一受体。我们将 基因序列与 基因融合，以便将表达的S蛋白递送至cDC1细胞。在小鼠中，用编码与Xcl1融合的S蛋白的质粒进行免疫，比单独用 质粒免疫显示出更强的抗体和抗原特异性T细胞免疫反应诱导作用。融合基因诱导产生的抗体还表现出更强的SARS-CoV-2野生型病毒和假病毒中和活性。Xcl1还增加了骨髓中长寿的抗体分泌浆细胞。这些初步结果表明，Xcl1可作为SARS-CoV-2疫苗的分子佐剂，并且我们的Xcl1-S融合DNA疫苗是一种潜在的COVID-19疫苗候选物，可用于进一步的转化研究。
