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

Mol Biotechnol. 2024 Jul;66(7):1718-1726. doi: 10.1007/s12033-023-00800-4. Epub 2023 Jul 10.

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.

Keywords: Adjuvant; Biodefense; CpG oligodeoxynucleotide; Protective immunity; Smallpox DNA vaccine; TLR9 ligand.

MeSH terms

  • Adjuvants, Immunologic* / administration & dosage
  • Animals
  • Antibodies, Viral / immunology
  • Female
  • Mice
  • Mice, Inbred BALB C*
  • Oligodeoxyribonucleotides* / administration & dosage
  • Oligodeoxyribonucleotides* / immunology
  • Smallpox Vaccine* / administration & dosage
  • Smallpox Vaccine* / genetics
  • Smallpox Vaccine* / immunology
  • Smallpox* / immunology
  • Smallpox* / prevention & control
  • Th2 Cells* / immunology
  • Toll-Like Receptor 9 / immunology
  • Vaccination / methods
  • Vaccines, DNA* / administration & dosage
  • Vaccines, DNA* / immunology
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology

Substances

  • Vaccines, DNA
  • Oligodeoxyribonucleotides
  • Smallpox Vaccine
  • CPG-oligonucleotide
  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Toll-Like Receptor 9