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Post-Vaccination Delivery of CpG ODNs Enhances the Th2-Associated Protective Immunity of the Smallpox DNA Vaccine

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Abstract

Potential threat of smallpox bioterrorism and concerns related to the adverse effects of currently licensed live-virus vaccines suggest the need to develop novel vaccines with better efficacy against smallpox. Use of DNA vaccines containing specific antigen-encoding plasmids prevents the risks associated with live-virus vaccines, offering a promising alternative to conventional smallpox vaccines. In this study, we investigated the efficiency of toll-like receptor (TLR) ligands in enhancing the immunogenicity of smallpox DNA vaccines. BALB/c mice were immunized with a DNA vaccine encoding the vaccinia virus L1R protein, along with the cytosine–phosphate–guanine (CpG) motif as a vaccine adjuvant, and their immune response was analyzed. Administration of B-type CpG oligodeoxynucleotides (ODNs) as TLR9 ligands 24 h after DNA vaccination enhanced the Th2-biased L1R-specific antibody immunity in mice. Moreover, B-type CpG ODNs improved the protective effects of the DNA vaccine against the lethal Orthopoxvirus challenge. Therefore, use of L1R DNA vaccines with CpG ODNs as adjuvants is a promising approach to achieve effective immunogenicity against smallpox infection.

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Acknowledgements

This work was supported by a grant from the Agency for Defense Development, Republic of Korea (UD180041GD, 211555-912664201).

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Authors and Affiliations

  1. R&D Center, ABION Inc., Seoul, Republic of Korea

    Min Hoon Lee, Hong Seok Choi, Na Young Kim, Euni Sim & Jun Young Choi

  2. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea

    Min Hoon Lee & Young Kee Shin

  3. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea

    Sungyoul Hong & Young Kee Shin

  4. Chem-Bio Technology Center, Agency for Defense Development, Daejeon, Republic of Korea

    Chi Ho Yu, Se Hun Gu, Dong Hyun Song & Gyueng Haeng Hur

  5. Bio-MAX/N-Bio, Seoul National University, Seoul, Republic of Korea

    Sungho Shin

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Contributions

Conceived and designed the experiments: Na Young Kim, Sungho Shin. Performed the experiments: Min Hoon Lee, Euni Sim, Hong Seok Choi, Sungyoul Hong. Analyzed the data: Min Hoon Lee, Na Young Kim, Hong Seok Choi, Jun Young Choi, Young Kee Shin, Chi Ho Yu, Se Hun Gu, Dong Hyun Song, Gyueng Haeng Hur, Sungho Shin. Contributed reagents/materials/analysis tools: Jun Young Choi. Wrote the paper: Sungho Shin.

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Correspondence to Sungho Shin.

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Conflict of Interest

Na Young Kim, Euni Sim, Jun Young Choi, and Young Kee Shin currently hold stock and Min Hoon Lee, Hong Seok Choi, Na Young Kim, and Jun Young Choi hold stock options in ABION Inc.

Ethics Approval

All animal studies were conducted under protocols approved by the Institutional Animal Care and Use Committee of Institution (approval ID: SNU001254, IACUC SNU-190325-1).

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Lee, M.H., Choi, H.S., Kim, N.Y. et al. Post-Vaccination Delivery of CpG ODNs Enhances the Th2-Associated Protective Immunity of the Smallpox DNA Vaccine. Mol Biotechnol 66, 1718–1726 (2024). https://doi.org/10.1007/s12033-023-00800-4

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