PEI‐PLGA nanoparticles significantly enhanced the immunogenicity of IsdB_137‐361 proteins from Staphylococcus aureus

Abstract

Introduction Staphylococcus aureus seriously threatens human and animal health. IsdB137‐361 of the iron surface determinant B protein (IsdB) from S. aureus exhibits the strong immunogenicity, but its immunoprotective effect is still to be further promoted. Because PEI‐PLGA nanoparticles are generated by PEI conjugate with PLGA to develop great potential as a novel immune adjuvant, the immunogenicity of IsdB137‐361 is likely be strengthened by PEI‐PLGA. Methods Here, PEI‐PLGA nanoparticles containing IsdB137‐361 proteins were prepared by optimizing the entrapment efficiency. Mice were immunized with IsdB137‐361‐PEI‐PLGA nanoparticles to assess their anti‐S. aureus effects. The level of IFN‐γ, IL‐4, IL‐17, and IL‐10 cytokines from spleen lymphocytes in mice and generation of the antibodies against IsdB137‐361 in serum was assessed by ELISA, the protective immune response was appraised by S. aureus challenge. Results IsdB137‐361 proteins loaded by PEI‐PLGA were able to stimulate effectively the proliferation of spleen lymphocytes and increase the secretion of IFN‐γ, IL‐4, IL‐17, and IL‐10 cytokine from spleen lymphocytes, and significantly enhance generation of the antibodies against IsdB137‐361 in serum, reduce the level of bacterial load in liver, spleen and kidney, and greatly improve the survival rate of mice after challenge. Conclusion These data showed that PEI‐PLGA nanoparticles can significantly enhance the immunogenicity of IsdB137‐361 proteins, and provide an important reference for the development of novel immune adjuvant.

A Unique Combination of Mn2+ and Aluminum Adjuvant Acted the Synergistic Effect

“…The bacterial load assay was carried out as previously described [ 27 , 28 ]. In brief, fourteen days after the last immunization, S. aureus strain Newman was used to inject intraperitoneally and infect the immunized mice.…”

“…Opsonophagocytosis assay was carried out according to [ 27 , 28 ]. In brief, wild-type (WT) mice were treated intraperitoneally with 1 mL (60 mg/mL) of thioglycolate solution for 72 h, and then, the peritoneal macrophages were collected and cultured in 6-well plates, and after 24 h, 30 μ L of serum in immunized mice was incubated with 1.5 × 10 6 CFU of S. aureus strain Newman at 37°C for 2 h. Then, the mixture was used to treat the macrophages, and after 4 h, these macrophages were incubated with gentamicin of 100 μ g/mL to kill the extracellular bacteria outside the macrophages, and after 1 h, the lysates of macrophages were obtained and cultured on TSA plates at 37°C for 12 h. Finally, the number of phagocytized bacteria was confirmed.…”

Gallic Acid-Modified Polyethylenimine–Polypropylene Carbonate–Polyethylenimine Nanoparticles: Synthesis, Characterization, and Anti-Periodontitis Evaluation

“…Due to its self-assembly behavior, PEI demonstrates significant potential for nanoparticle formation with various hydrophobic polymers, including poly­(methyl methacrylate) (PMMA), poly­(ε-caprolactone)-pluronic-poly­(ε-caprolactone) (PCFC), poly­(caprolactone) (PCL), and poly­(lactic acid) (PDL), and can even be combined with hydrophilic poly­(ethylene glycol) (PEG) to form more complex nanoparticles. − PEI is extensively utilized in the synthesis of amphiphilic copolymers with hydrophobic polymers, leading to the formation of nanoparticles. Notably, nanoparticles derived from the hydrophobic polylactic acid-hydroxyacetic acid copolymer (PLGA)-PEI have exhibited promising applications in immunomodulation, siRNA delivery, DNA transfection, exosome delivery, and loading of tumor-targeting drugs. − This versatility is attributed to the high number of amino groups in PEI, which facilitates modifications. However, the highly positively charged structure of these amines renders cells more susceptible to damage, rendering PEI notoriously cytotoxic. − As a result, reducing the cytotoxic effects of PEI is a primary consideration in the design of PEI nanoparticles …”

“…Notably, nanoparticles derived from the hydrophobic polylactic acid-hydroxyacetic acid copolymer (PLGA)-PEI have exhibited promising applications in immunomodulation, siRNA delivery, DNA transfection, exosome delivery, and loading of tumor-targeting drugs. 20 − 23 This versatility is attributed to the high number of amino groups in PEI, which facilitates modifications. However, the highly positively charged structure of these amines renders cells more susceptible to damage, rendering PEI notoriously cytotoxic.…”