Comparison of immunogenicity and protection efficacy of self-amplifying and circular mRNA vaccines against SARS-CoV-2
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.
Authors
- C. T. Ranjith-Kumar (ORCID: https://orcid.org/0009-0000-9686-8231)
- Milan Surjit (ORCID: https://orcid.org/0000-0001-8435-3257)
- Tripti Shrivastava (ORCID: https://orcid.org/0000-0001-6942-1274)
- Shailendra Mani (ORCID: https://orcid.org/0000-0001-8541-8315)
- Tejeswara Rao Asuru (ORCID: https://orcid.org/0009-0000-6745-9682)
- Debasis Nayak (ORCID: https://orcid.org/0000-0002-4762-4553)
- Gaurav Batra (ORCID: https://orcid.org/0000-0003-1669-4310)
- Oinam Ningthemmani Singh
- Souvick Chattopadhyay (ORCID: https://orcid.org/0000-0002-5198-4615)
- Umang Berry
- Sriram Narayanan (ORCID: https://orcid.org/0000-0003-4658-0883)
- Garima Joshi (ORCID: https://orcid.org/0000-0002-3039-574X)
- Mahima Tiwari (ORCID: https://orcid.org/0000-0003-3707-6992)
- Puneet Srivastava (ORCID: https://orcid.org/0000-0002-3685-7781)
- Prasenjit Guchhait (ORCID: https://orcid.org/0000-0002-6601-6692)
- Kannan Chandrasekar (ORCID: https://orcid.org/0000-0003-0453-167X)
- Bhisma Narayan Panda
- Farha Mehdi
Institutions
- Guru Gobind Singh Indraprastha University (IN)
- Translational Health Science and Technology Institute (IN)
- Indian Institute of Science Education and Research, Bhopal (IN)
- Regional Centre for Biotechnology (IN)
Publication Details
- Journal
- iScience
- Published
- 2025-09-04
- DOI
- https://doi.org/10.1016/j.isci.2025.113498
- Citations
- 2
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 2.79
Funders
- Biotechnology Industry Research Assistance Council