Dormeshkin Dmitri, Katsin Mikalai, Stegantseva Maria, Golenchenko Sergey, Shapira Michail, Dubovik Simon, Lutskovich Dzmitry, Kavaleuski Anton, Meleshko Alexander
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, 220084 Minsk, Belarus.
Immunofusion, LLC, 210004 Vitebsk, Belarus.
Vaccines (Basel). 2023 May 23;11(6):1014. doi: 10.3390/vaccines11061014.
The potential of immune-evasive mutation accumulation in the SARS-CoV-2 virus has led to its rapid spread, causing over 600 million confirmed cases and more than 6.5 million confirmed deaths. The huge demand for the rapid development and deployment of low-cost and effective vaccines against emerging variants has renewed interest in DNA vaccine technology. Here, we report the rapid generation and immunological evaluation of novel DNA vaccine candidates against the Wuhan-Hu-1 and Omicron variants based on the RBD protein fused with the Potato virus X coat protein (PVXCP). The delivery of DNA vaccines using electroporation in a two-dose regimen induced high-antibody titers and profound cellular responses in mice. The antibody titers induced against the Omicron variant of the vaccine were sufficient for effective protection against both Omicron and Wuhan-Hu-1 virus infections. The PVXCP protein in the vaccine construct shifted the immune response to the favorable Th1-like type and provided the oligomerization of RBD-PVXCP protein. Naked DNA delivery by needle-free injection allowed us to achieve antibody titers comparable with mRNA-LNP delivery in rabbits. These data identify the RBD-PVXCP DNA vaccine platform as a promising solution for robust and effective SARS-CoV-2 protection, supporting further translational study.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒中免疫逃逸突变积累的可能性导致其迅速传播，造成超过6亿例确诊病例和超过650万例确诊死亡。对快速开发和部署针对新出现变体的低成本有效疫苗的巨大需求，重新引发了人们对DNA疫苗技术的兴趣。在此，我们报告了基于与马铃薯X病毒外壳蛋白（PVXCP）融合的受体结合域（RBD）蛋白，针对武汉-胡-1和奥密克戎变体的新型DNA疫苗候选物的快速生成和免疫学评估。在两剂方案中使用电穿孔递送DNA疫苗可在小鼠中诱导高抗体滴度和强烈的细胞反应。针对该疫苗奥密克戎变体诱导的抗体滴度足以有效预防奥密克戎和武汉-胡-1病毒感染。疫苗构建体中的PVXCP蛋白将免疫反应转变为有利的类似Th1型，并促进了RBD-PVXCP蛋白的寡聚化。通过无针注射递送裸DNA使我们在兔中获得了与mRNA-脂质纳米颗粒（LNP）递送相当的抗体滴度。这些数据表明，RBD-PVXCP DNA疫苗平台是实现强大而有效的SARS-CoV-2防护的一个有前景的解决方案，支持进一步的转化研究。
