Abstract
Vaccination strategies for Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA) infections have attracted much research attention. Recent efforts have been made to select manganese transport protein C, or manganese binding surface lipoprotein C (MntC), which is a metal ion associated with pathogen nutrition uptake, as potential candidates for an S. aureus vaccine. Although protective humoral immune responses to MntC are well-characterised, much less is known about detailed MntC-specific B cell epitope mapping and particularly epitope vaccines, which are less-time consuming and more convenient. In this study, we generated a recombinant protein rMntC which induced strong antibody response when used for immunisation with CFA/IFA adjuvant. On the basis of the results, linear B cell epitopes within MntC were finely mapped using a series of overlapping synthetic peptides. Further studies indicate that MntC113-136, MntC209-232, and MntC263-286 might be the original linear B-cell immune dominant epitope of MntC, furthermore, three-dimensional (3-d) crystal structure results indicate that the three immunodominant epitopes were displayed on the surface of the MntC antigen. On the basis of immunodominant MntC113-136, MntC209-232, and MntC263-286 peptides, the epitope vaccine for S. aureus induces a high antibody level which is biased to TH2 and provides effective immune protection and strong opsonophagocytic killing activity in vitro against MRSA infection. In summary, the study provides strong proof of the optimisation of MRSA B cell epitope vaccine designs and their use, which was based on the MntC antigen in the development of an MRSA vaccine.
Highlights
Staphylococcus aureus (S. aureus) is an opportunistic bacterial pathogen responsible for a diverse range of human infection diseases [1] [2], including minor skin infections and lifethreatening diseases, such as bacteraemia, pneumonia, endocarditis, osteomyelitis, sepsis, and wound infections [3] [4] [5]
Infections of methicillin-resistant S. aureus (MRSA) that are resistant to vancomycin or multiantibiotic strategies are endemic in many health care institutions and communities [7]
We found that immunised purified manganese binding surface lipoprotein C (MntC) protein is responsible for eliciting anti-MntC IgG immune responses as an immunotherapeutic agent and that it effectively increased immune protection rates against MRSA in a BALB/c systemic infection mouse model, which probably functioned through the B cell immunodominant epitopes of MntC
Summary
Staphylococcus aureus (S. aureus) is an opportunistic bacterial pathogen responsible for a diverse range of human infection diseases [1] [2], including minor skin infections and lifethreatening diseases, such as bacteraemia, pneumonia, endocarditis, osteomyelitis, sepsis, and wound infections [3] [4] [5]. These diseases are associated with a high rate of morbidity and mortality, imposing an increasingly high burden on health care resources [6]. Anti-MntC monoclonal antibodies have been identified as binding to S. aureus cells [16], MntC might be a potential therapeutic target for the development of antibiotics, and MntC could define potential antigen combinations for multicomponent vaccines [17]
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