title: Induction of death receptor CD95 and co-stimulatory molecules CD80 and CD86 by meningococcal capsular polysaccharide-loaded vaccine nanoparticles.
abstract: Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis, and its capsular polysaccharides (CPS) are a major virulence factor in meningococcal infections and form the basis for serogroup designation and protective vaccines. We formulated a novel nanovaccine containing meningococcal CPS as an antigen encapsulated in albumin-based nanoparticles (NPs) that does not require chemical conjugation to a protein carrier. These nanoparticles are taken up by antigen-presenting cells and act as antigen depot by slowly releasing the antigen. In this study, we determined the ability of CPS-loaded vaccine nanoparticles to induce co-stimulatory molecules, namely CD80, CD86, and CD95 that impact effective antigen presentation. Co-stimulatory molecule gene induction and surface expression on macrophages and dendritic cells pulsed with meningococcal CPS-loaded nanoparticles were investigated using gene array and flow cytometry methods. Meningococcal CPS-loaded NP significantly induced the surface protein expression of CD80 and CD86, markers of dendritic cell maturation, in human THP-1 macrophages and in murine dendritic cells DC2.4 in a dose-dependent manner. The massive upregulation was also observed at the gene expression. However, high dose of CPS-loaded NP, but not empty NP, induced the expression of death receptor CD95 (Fas) leading to reduced TNF-α release and reduction in cell viability. The data suggest that high expression of CD95 may lead to death of antigen-presenting cells and consequently suboptimal immune responses to vaccine. The CPS-loaded NP induces the expression of co-stimulatory molecules and acts as antigen depot and can spare antigen dose, highly desirable criteria for vaccine formulations.
authors: Department of Pharmaceutical Sciences, School of Pharmacy, Union University, Jackson, Tennessee, 38305, USA.
authors: Ruhi V
authors: RV
authors: Ubale
authors: Rikhav P
authors: RP
authors: Gala
authors: Susu M
authors: SM
authors: Zughaier
authors: Martin J
authors: MJ
authors: D'Souza
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism*; D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D022401:Meningococcal Vaccines / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D053758:Nanoparticles; D036103:Nanotechnology; D009345:Neisseria meningitidis / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; C491901:FAS protein, human; C491899:Fas protein, mouse; D022401:Meningococcal Vaccines; D011135:Polysaccharides, Bacterial; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide