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Immunogenicity and protective efficacy of recombinant alkaline shock protein 23 from Staphylococcus aureus in a murine model.

ABSTRACT: The diversity and severity of infections caused and the rapid emergence of antibiotic resistance necessitates the development of a vaccine against Staphylococcus aureus. None of the antigens tried as vaccine candidates so far has been translated into a clinically viable vaccine. Recent research data suggest that antigens with the potential to activate cell mediated immunity along with humoral immunity would be the key to the development of a vaccine. Alkaline shock protein 23, a membrane-anchored protein involved in the stress response, has been identified as a CD4+ T cell antigen from S. aureus. In the present study, we report the evaluation of immunogenicity and protective efficacy of a recombinant alkaline shock protein 23 from S. aureus in mouse models. The gene coding for the protein was cloned and expressed in Escherichia coli, purified using immobilized metal iron affinity chromatography, sequence-confirmed using mass spectrometry and intraperitoneally administered to BALB/c mice. Serum titers of IgG, IgG1, and IgG2a in response to the protein were measured on post-immunization days 21, 35 and 42 using indirect ELISA and compared to control mice injected with PBS. Our results showed that the protein induced significantly higher (p < 0.01) antibody responses in immunized mice compared to the control mice. The mean serum antibody titers of IgG, IgG1 and IgG2a three weeks after the last immunization were found to be 25600, 25600 and 12800 respectively. Moreover, we found that immunization with Asp23 protected mice from a lethal dose of S. aureus strain USA300.

SUBMITTER: Francis D

PROVIDER: S-EPMC6384426 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Immunogenicity and protective efficacy of recombinant alkaline shock protein 23 from <i>Staphylococcus aureus</i> in a murine model.

Francis Dileep D Kuyyalil Surekha S

Central-European journal of immunology 20181231 4

The diversity and severity of infections caused and the rapid emergence of antibiotic resistance necessitates the development of a vaccine against Staphylococcus aureus. None of the antigens tried as vaccine candidates so far has been translated into a clinically viable vaccine. Recent research data suggest that antigens with the potential to activate cell mediated immunity along with humoral immunity would be the key to the development of a vaccine. Alkaline shock protein 23, a membrane-anchore ...[more]

PMID: 30799984

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Project description:IntroductionThe refractory and recurrent nature of chronic staphylococcal osteomyelitis may be due, at least in part, to the ability of Staphylococcus aureus to invade and persist within bone-forming osteoblasts. However, osteoblasts are now recognized to respond to S. aureus infection and produce numerous immune mediators and bone regulatory factors that can shape the host response. Type I interferons (IFNs) are best known for their antiviral effects, but it is becoming apparent that they impact host susceptibility to a wide range of pathogens including S. aureus.MethodsHere, we have assessed the local expression of IFN-β by specific capture ELISA in an established in vivo mouse model of staphylococcal osteomyelitis. RNA Tag-Seq analysis, specific capture ELISAs, and/or immunoblot analyses, were then used to assess the expression of type I IFNs and select IFN stimulated genes (ISGs) in S. aureus infected primary murine osteoblasts. The effect of IFN-β on intracellular S. aureus burden was assessed in vitro following recombinant cytokine treatment by serial colony counts of liberated bacteria.ResultsWe report the presence of markedly elevated IFN-β levels in infected bone tissue in a mouse model of staphylococcal osteomyelitis. RNA Tag-Seq analysis of S. aureus infected osteoblasts showed enrichment of genes associated with type I IFN signaling and ISGs, and elevated expression of mRNA encoding IFN-β and ISG products. IFN-β production was confirmed with the demonstration that S. aureus induces its rapid and robust release by osteoblasts in a dose-dependent manner. Furthermore, we showed increased protein expression of the ISG products IFIT1 and IFIT3 by infected osteoblasts and demonstrate that this occurs secondary to the release of IFN-β by these cells. Finally, we have determined that exposure of S. aureus-infected osteoblasts to IFN-β markedly reduces the number of viable bacteria harbored by these cells.DiscussionTogether, these findings indicate an ability of osteoblasts to respond to bacteria by producing IFN-β that can act in an autocrine and/or paracrine manner to elicit ISG expression and mitigate S. aureus infection.

Dataset Information

Immunogenicity and protective efficacy of recombinant alkaline shock protein 23 from Staphylococcus aureus in a murine model.

Publications

Immunogenicity and protective efficacy of recombinant alkaline shock protein 23 from <i>Staphylococcus aureus</i> in a murine model.

Similar Datasets

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