Singh Oinam Ningthemmani, Berry Umang, Joshi Garima, Asuru Tejeswara Rao, Chandrasekar Kannan, Narayanan Sriram, Srivastava Puneet, Tiwari Mahima, Chattopadhyay Souvick, Mehdi Farha, Panda Bhisma Narayan, Nayak Debasis, Mani Shailendra, Shrivastava Tripti, Batra Gaurav, Ranjith-Kumar C T, Guchhait Prasenjit, Surjit Milan
Centre for Virus Research, Therapeutics and Vaccines, Translational Health Science and Technology Institute, National Capital Region Biotech Science Cluster, Faridabad, Haryana, India.
Regional Centre for Biotechnology, National Capital Region Biotech Science Cluster, Faridabad, Haryana, India.
iScience. 2025 Sep 4;28(10):113498. doi: 10.1016/j.isci.2025.113498. eCollection 2025 Oct 17.
Recent advances in vaccine technology have positioned messenger RNA (mRNA) vaccines as safe and reliable options for human use. Conventionally, mRNA vaccines were designed using linear or self-amplifying mRNA (SAM), the latter considered to be superior. Subsequent studies on Circular mRNA (Circ-RNA) vaccines proved their efficacy. Here, we compared the efficacy of SAM- and Circ-RNA vaccines using the SARS-CoV-2-RBD (receptor binding domain) antigen. Both SAM-RBD and Circ-RBD induced a comparable anti-RBD IgG titer and virus-neutralizing antibody titer. However, the latter induced a higher memory T cell response. The Circ-RBD vaccine is stable for 4 weeks at 4°C. A bivalent vaccine containing Circ-RBD of both delta and omicron SARS-CoV-2 variants potently neutralized these viruses. These findings demonstrate Circ-RNA-RBD as an excellent vaccine candidate against COVID-19 and also provide a platform for developing bivalent Circ-RNA vaccine candidates against SARS-CoV-2 or other viruses with rapidly emerging variants.
疫苗技术的最新进展已将信使核糖核酸（mRNA）疫苗定位为供人类使用的安全可靠选择。传统上，mRNA疫苗是使用线性或自我扩增mRNA（SAM）设计的，后者被认为更具优势。随后对环状mRNA（Circ-RNA）疫苗的研究证明了它们的有效性。在此，我们使用严重急性呼吸综合征冠状病毒2受体结合域（SARS-CoV-2-RBD）抗原比较了SAM疫苗和Circ-RNA疫苗的有效性。SAM-RBD和Circ-RBD均诱导了相当的抗RBD IgG滴度和病毒中和抗体滴度。然而，后者诱导了更高的记忆T细胞反应。Circ-RBD疫苗在4°C下可稳定保存4周。一种包含德尔塔和奥密克戎SARS-CoV-2变体的Circ-RBD的二价疫苗能有效中和这些病毒。这些发现证明Circ-RNA-RBD是一种针对2019冠状病毒病的优秀疫苗候选物，也为开发针对SARS-CoV-2或其他具有快速出现变体的病毒的二价Circ-RNA疫苗候选物提供了一个平台。
