The novel combinations of CTB, CpG, and aluminum hydroxide significantly enhanced the immunogenicity of clumping factor A 221-550 of Staphylococcus aureus

Biosci Biotechnol Biochem. 2020 Sep;84(9):1846-1855. doi: 10.1080/09168451.2020.1771170. Epub 2020 Jun 5.

Abstract

Here, we prepared the novel combined adjuvants, CTB as intra-molecular adjuvant, CpG and aluminum hydroxide (Alum) to strengthen the immunogenicity of clumping factor A221-550 of Staphylococcus aureus (S. aureus). The protein-immunoactive results showed CTB-ClfA221-550 elicited the strong immune responses to serum from mice immunized with CTB and ClfA221-550, respectively. The mice immunized with CTB-ClfA221-550 plus CpG and Alum adjuvant exhibited significantly stronger CD4+ T cell responses for IFN-γ, IL-2, IL-4, and IL-17 and displayed the higher proliferation response of splenic lymphocytes than the control groups, in addition, these mice generated the strongest humoral immune response against ClfA221-550 among all groups. Our results also showed CTB-ClfA221-550 plus CpG and Alum adjuvant obviously increased the survival percentage of the mice challenged by S. aureus. These data suggested that the novel combined adjuvants, CTB, CpG, and Alum, significantly enhance the immune responses triggered with ClfA221-550, and could provide a new approach against infection of S. aureus.

Abbreviations: CTB: Cholera Toxin B; CpG: Cytosine preceding Guanosine; ODN: Oligodeoxynucleotides; Alum: Aluminum hydroxide; TRAP: Target of RNAIII-activating Protein; TLR9: Toll-like Receptor 9; TMB: 3, 3', 5, 5'-tetramethylbenzidine; mAbs: Monoclonal Antibodies; OD: Optical Densities; S. aureus: Staphylococcus aureus; ClfA: Clumping factor A; FnBPA: Fibronection-binding protein A; IsdB: Iron-regulated surface determinant B; SasA: Staphylococcus aureus Surface Protein A; GapC: Glycer-aldehyde-3-phosphate dehydrogenase-C.

Keywords: CTB; CTB-ClfA221-550; CpG; aluminum hydroxide; the combined adjuvants.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Aluminum Hydroxide / pharmacology*
  • Animals
  • Cell Proliferation / drug effects
  • Cholera Toxin / pharmacology*
  • Coagulase / immunology*
  • Drug Interactions
  • Immunization
  • Lymphocytes / cytology
  • Lymphocytes / drug effects
  • Mice
  • Oligodeoxyribonucleotides / pharmacology

Substances

  • Adjuvants, Immunologic
  • ClfA protein, Staphylococcus aureus
  • Coagulase
  • Oligodeoxyribonucleotides
  • Aluminum Hydroxide
  • Cholera Toxin