Abstract
No vaccine against methicillin-resistant Staphylococcus aureus (MRSA) has been currently approved for use in humans. Staphylococcus enterotoxin B (SEB) is one of the most potent MRSA exotoxins. In the present study, we evaluated the efficacy and immunologic mechanisms of an SEB multiple B-cell epitope vaccine against MRSA infection. Synthetic overlapping peptide ELISA identified three novel B-cell immunodominant SEB epitopes (in addition to those previously known): SEB31–48, SEB133–150, and SEB193–210. Six B-cell immunodominant epitopes (amino acid residues 31–48, 97–114, 133–150, 193–210, 205–222, and 247–261) were sufficient to induce robust IgG1/IgG2b-specific protective responses against MRSA infection. Therefore, we constructed a recombinant MRSA SEB-specific multiple B-cell epitope vaccine Polypeptides by combining the six SEB immunodominant epitopes and demonstrated its ability to induce a robust SEB-specific IgG1 response to MRSA, as well as a Th2-directing isotype response. Moreover, Polypeptides-induced antisera stimulated synergetic opsonophagocytosis killing of MRSA. Most importantly, Polypeptides was more effective at clearing the bacteria in MRSA-infected mice than the whole SEB antigen, and was able to successfully protect mice from infection by various clinical MRSA isolates. Altogether, these results support further evaluation of the SEB multiple B-cell epitope-vaccine to address MRSA infection in humans.
Highlights
Majority of methicillin-resistant S. aureus (MRSA) isolates in very high concentrations[11,12]
We had suggested that there might be other SEB B-cell epitope-specific response during MRSA infection that were different with Recombinant mutant SEB (rSEB) immunization
Linear B-cell epitope mapping of SEB was further determined by an ELISA with overlapping 18-mer peptides and antisera obtained from rSEB-immunised mice following MRSA challenge
Summary
Majority of MRSA isolates in very high concentrations[11,12]. According to NCBI-BLAST, the SEB protein sequence is conserved across many prevalent MRSA isolates including N31513, ST22814, Mu315, Mu5016, JH1, and JH917. Whole antigen vaccines are not as potent as epitope-specific vaccines[23], since only a few immunodominant epitopes are sufficient to induce a protective response[24,25]. Since previous studies have confirmed that immunodominant SEB peptide vaccination can convey a potent humoral immune response[26], this methodology may aid in the optimisation of MRSA vaccine strategy. We have mapped the B-cell immunodominant epitopes in SEB by synthetic overlapping peptide ELISA, combined these immunogens to construct a single SEB-specific multiple B-cell epitope vaccine (Polypeptides), and confirmed the vaccine’s ability to stimulate the synergetic opsonophagocytosis of MRSA bacteria and protect mice from infection by various clinical MRSA isolates
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