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 me...

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Bibliographic Details
Published in:The AAPS journal 2014-09, Vol.16 (5), p.986-993
Main Authors: Ubale, Ruhi V., Gala, Rikhav P., Zughaier, Susu M., D’Souza, Martin J.
Format: Article
Language:English
Subjects:
Animals
B7-1 Antigen - genetics
B7-1 Antigen - metabolism
B7-2 Antigen - genetics
B7-2 Antigen - metabolism
Biochemistry
Biomedical and Life Sciences
Biomedicine
Biotechnology
Cell Line
Cell Survival - drug effects
Chemistry, Pharmaceutical
Dendritic Cells - drug effects
Dendritic Cells - immunology
Dendritic Cells - metabolism
Dose-Response Relationship, Drug
fas Receptor - genetics
fas Receptor - metabolism
Humans
Macrophages - drug effects
Macrophages - immunology
Macrophages - metabolism
Meningococcal Vaccines - chemistry
Meningococcal Vaccines - immunology
Meningococcal Vaccines - pharmacology
Mice
Nanoparticles
Nanotechnology
Neisseria meningitidis - immunology
Nitric Oxide - metabolism
Pharmacology/Toxicology
Pharmacy
Polysaccharides, Bacterial - chemistry
Polysaccharides, Bacterial - immunology
Polysaccharides, Bacterial - pharmacology
Research Article
RNA, Messenger - metabolism
Serum Albumin, Bovine - chemistry
Technology, Pharmaceutical - methods
Theme: Nanoparticles in Vaccine Delivery
Tumor Necrosis Factor-alpha - metabolism
Up-Regulation
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Summary: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.
ISSN:1550-7416
1550-7416
DOI:10.1208/s12248-014-9635-2