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Polyethyleneimine (PEI) is a potent mucosal a djuvant for glycoprotein antigents. Take home message: The efficacy of PEI as a mucosal adjuvant and involved adaptive immune activation. Yan Mei Mar 3rd. Nature Biotechnology, 2012, 30 (9), 883-890 . PEI. Chemical Structure.
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Polyethyleneimine (PEI) is a potent mucosal adjuvant for glycoprotein antigents Take home message: The efficacy of PEI as a mucosal adjuvant and involved adaptive immune activation. Yan Mei Mar 3rd Nature Biotechnology, 2012, 30 (9), 883-890
PEI Chemical Structure PEI forms complexes with nucleic acids through electrostatic interactions forming nano-scale polyplexes. These polyplexes bind negatively charged cell surface and finally enter the cell. In addition, PEI has been used to increase the immunogenicity of DNA vaccines Toxicity A single dose of antigen with either 20 or 40 micro gram PEI was safe.
Mucosal Adjuvant Activity of PEI Gp140- antigen CTB- mucosal adjuvant The antigen-specific IgG endpoint titers of PEI ,CTB and CpG were significantly higher than gp140 alone or formulated with PGLA. The antigen-specific IgG titers in the serum were 100 times higher when gp140 was combine with PEI than alone and 6 times higher than those combined with CTB. Investigated the IgA levels in vaginal lavages. The mouse immunized with antigen in PEI were completely protected from weight loss. PEI is a effective mucosal adjuvant !!
Adaptive Immune Activation – in vitro The adaptive immunity induced by PEI suggested antigen targeting to APC either directly or indirectly by targeting to mucosal epithelial cells followed by cell death and APC uptake or both. To test whether gp140-PEI particles were targeted for APC uptake in vitro, they treated bone marrow-derived dendritic cells with fluorochrome-labeled gp140 or gp140-PEI. Gp140 and PEI led to intracellular uptake of the particulate complexes.
Adaptive Immune Activation – in vivo Disaggregatednasal-associated lymphiod tissue (NALT) Draining cervical lymph node (DCLN) PEI significantly enhanced gp140 uptake by epithelial cells and microfoldcells. The PEI-mediated antigen targeting was accompanied by modest transient recruitment of neutrophils into the NALT. Gp140 was primarily found associated with dendritic cells in DCLN, and PEI mediated significantly recruitment of dendritic cells and B cells.
Conclusion Different PEI forms have potent adjuvant activity for viral subunit glycoprotein antigens. PEI associates with glycoprotein antigen and complexes are targeted to, and taken up by APC. These then process the antigen via the HLA class-II pathway leading to activation of Th2 cells. Th2 cells provide help for B cells to produce antibodies against the antigen.