Improved protective efficacy of a chimeric Staphylococcus aureus vaccine candidate iron-regulated surface determinant B ( N 126- P 361) -target of RNAIII activating protein in mice

Microbiol Immunol. 2013 Dec;57(12):857-64. doi: 10.1111/1348-0421.12106.

Abstract

The pathogen Staphylococcus aureus causes a wide range of serious infections, necessitating urgent development of a vaccine against this organism. However, currently developed vaccines are relatively ineffective because of the limited antigenic component that is contained in the vaccine formulations. To develop an effective S. aureus candidate vaccine, overlapping PCR was used to add the truncated immunodominant antigen iron-regulated surface determinant B (IsdB)(N126-P361) (tIsdB) to the N-terminal of intact antigen target of RNAIII activating protein (TRAP) and thus construct a tIsdB-TRAP chimera. The humoral and cellular immune responses against tIsdB-TRAP were compared with those against single or combined formulations. tIsdB-TRAP elicited significantly stronger humoral responses in mice (P < 0.05). As to cellular immune responses in mice, the tIsdB-TRAP group resulted in a greater IL-4 response than did other groups (P < 0.05). Greater amounts of IL-2 and IFN-γ were found in the tIsdB-TRAP group. Mouse challenge also showed that tIsdB-TRAP provided better protection against S. aureus than did the control groups. These results suggest that this chimeric protein may be a promising pathogen target for further vaccine development.

Keywords: Chimeric vaccine; Staphylococcus aureus; target of RNAIII activating protein; truncated immunodominant antigen iron-regulated surface determinant B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antibodies, Bacterial / blood
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Biological Assay
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / immunology*
  • Disease Models, Animal
  • Female
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-4 / metabolism
  • Leukocytes, Mononuclear / immunology
  • Mice
  • Mice, Inbred BALB C
  • Phosphoproteins / genetics
  • Phosphoproteins / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Staphylococcal Infections / prevention & control*
  • Staphylococcal Vaccines / administration & dosage*
  • Staphylococcal Vaccines / genetics
  • Staphylococcal Vaccines / immunology*
  • Survival Analysis
  • Vaccination / methods*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • Antibodies, Bacterial
  • Bacterial Proteins
  • Cation Transport Proteins
  • Interleukin-2
  • IsdB protein, Staphylococcus aureus
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • Staphylococcal Vaccines
  • TRAP protein, Staphylococcus
  • Vaccines, Synthetic
  • Interleukin-4
  • Interferon-gamma