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Induction of Death Receptor CD95 and Co-stimulatory Molecules CD80 and CD86 by Meningococcal Capsular Polysaccharide-Loaded Vaccine Nanoparticles

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  • Theme: Nanoparticles in Vaccine Delivery
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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.

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ACKNOWLEDGMENTS

This work is supported in part by grants from Emory-Egleston Children’s Research Center and Center for Pediatric Nanomedicine of Emory + Children’s Pediatrics Research Center to S.M.Z. The authors are grateful to Dr. Seshu Gudlavelleti for providing meningococcal vaccine-grade serogroup A capsular polysaccharides.

Conflict of interest

The authors have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, Union University, Jackson, Tennessee, 38305, USA

    Ruhi V. Ubale

  2. Vaccine Nanotechnology Laboratory, Department of Pharmaceutical Science, College of Pharmacy, Mercer University, 3001 Mercer University Drive, Atlanta, Georgia, 30341, USA

    Rikhav P. Gala & Martin J. D’Souza

  3. Department of Microbiology and Immunology and Veterans Affairs Medical Center, Emory University School of Medicine, VAMC (151-I), 1670 Clairmont Road, Atlanta, Georgia, 30033, USA

    Susu M. Zughaier

Authors
  1. Ruhi V. Ubale
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  2. Rikhav P. Gala
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  3. Susu M. Zughaier
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  4. Martin J. D’Souza
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Corresponding authors

Correspondence to Susu M. Zughaier or Martin J. D’Souza.

Additional information

Guest Editor: Aliasger K. Salem

Ruhi V. Ubale and Rikhav P. Gala have equally contributed to this work.

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Ubale, R.V., Gala, R.P., Zughaier, S.M. et al. Induction of Death Receptor CD95 and Co-stimulatory Molecules CD80 and CD86 by Meningococcal Capsular Polysaccharide-Loaded Vaccine Nanoparticles. AAPS J 16, 986–993 (2014). https://doi.org/10.1208/s12248-014-9635-2

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