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Title: Enhancement of antigen-specific CD4+ and CD8+ T cell responses using a self-assembled biologic nanolipoprotein particle vaccine

Journal Article · · Vaccine
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  1. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division
  2. Loyola Univ. Medical Center, Maywood, IL (United States). Dept. of Microbiology & Immunology
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To address the need for vaccine platforms that induce robust cell-mediated immunity, we investigated the potential of utilizing self-assembling biologic nanolipoprotein particles (NLPs) as an antigen and adjuvant delivery system to induce antigen-specific murine T cell responses. Here, we utilized OT-I and OT-II TCR-transgenic mice to investigate the effects of NLP-mediated delivery of the model antigen ovalbumin (OVA) on T cell activation. Delivery of OVA with the TLR4 agonist monophosphoryl lipid A (MPLA) in the context of NLPs significantly enhanced the activation of both CD4+ and CD8+ T cells in vitro compared to co-administration of free OVA and MPLA. Upon intranasal immunization of mice harboring TCR-transgenic cells, NLPs enhanced the adjuvant effects of MPLA and the in vivo delivery of OVA, leading to significantly increased expansion of CD4+ and CD8+ T cells in lung-draining lymph nodes. Therefore, NLPs are a promising vaccine platform for inducing T cell responses following intranasal administration.

Research Organization:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Sponsoring Organization:
USDOE Office of Electricity (OE), Advanced Grid Research & Development. Power Systems Engineering Research
Grant/Contract Number:
AC52-07NA27344
OSTI ID:
1409999
Alternate ID(s):
OSTI ID: 1397843
Report Number(s):
LLNL-JRNL-724260
Journal Information:
Vaccine, Vol. 35, Issue 11; ISSN 0264-410X
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 13 works
Citation information provided by
Web of Science

References (24)

T-cell-inducing vaccines - what’s the future: T-cell vaccines journal December 2011
New horizons in adjuvants for vaccine development journal January 2009
Vaccine adjuvants revisited journal May 2007
Micro and Nanoparticle-Based Delivery Systems for Vaccine Immunotherapy: An Immunological and Materials Perspective journal December 2012
Nanoparticle vaccines journal January 2014
Enhanced and prolonged cross-presentation following endosomal escape of exogenous antigens encapsulated in biodegradable nanoparticles journal January 2006
Enhancement of Dendritic Cell Antigen Cross-Presentation by CpG DNA Involves Type I IFN and Stabilization of Class I MHC mRNA journal August 2005
Evaluation of Nanolipoprotein Particles (NLPs) as an In Vivo Delivery Platform journal March 2014
The use of nanolipoprotein particles to enhance the immunostimulatory properties of innate immune agonists against lethal influenza challenge journal December 2013
Colocalized Delivery of Adjuvant and Antigen Using Nanolipoprotein Particles Enhances the Immune Response to Recombinant Antigens journal January 2013
A Trifunctional Dextran-Based Nanovaccine Targets and Activates Murine Dendritic Cells, and Induces Potent Cellular and Humoral Immune Responses In Vivo journal December 2013
pH-Responsive Nanoparticle Vaccines for Dual-Delivery of Antigens and Immunostimulatory Oligonucleotides journal April 2013
Nanoparticle size influences the magnitude and quality of mucosal immune responses after intranasal immunization journal December 2012
Characterization and Purification of Polydisperse Reconstituted Lipoproteins and Nanolipoprotein Particles journal July 2009
Quantifying size distributions of nanolipoprotein particles with single-particle analysis and molecular dynamic simulations journal April 2008
Kinetic Analysis of His-Tagged Protein Binding to Nickel-Chelating Nanolipoprotein Particles journal July 2010
Immobilization of His-Tagged Proteins on Nickel-Chelating Nanolipoprotein Particles journal March 2009
Reversal of Autoimmunity by Boosting Memory-like Autoregulatory T Cells journal April 2010
Expanding antigen-specific regulatory networks to treat autoimmunity journal February 2016
Repressing Immunity in Autoimmune Disease journal May 2016
TLR and Nucleotide-Binding Oligomerization Domain-like Receptor Signals Differentially Regulate Exogenous Antigen Presentation journal December 2011
Presentation of Exogenous Protein Antigens on Major Histocompatability Complex Class I Molecules by Dendritic Cells: Pathway of Presentation and Regulation by Cytokines journal August 1997
Antigen delivery by α 2 -macroglobulin enhances the cytotoxic T lymphocyte response journal August 2009
The Human Cancer Antigen Mesothelin Is More Efficiently Presented to the Mouse Immune System when Targeted to the DEC-205/CD205 Receptor on Dendritic Cells journal September 2009

Cited By (2)

Lipid composition dictates serum stability of reconstituted high-density lipoproteins: implications for in vivo applications journal January 2018
Extent of MHC Clustering Regulates Selectivity and Effectiveness of T Cell Responses journal December 2018

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
77 NANOSCIENCE AND NANOTECHNOLOGY
Nanolipoprotein
Nanoparticle
Intranasal
Vaccine
T cell activation
Nanodisc