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

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.
Authors:
 [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [2] ;  [1] ;  [2] ;  [1]
  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
Publication Date:
Report Number(s):
LLNL-JRNL-724260
Journal ID: ISSN 0264-410X
Grant/Contract Number:
AC52-07NA27344
Type:
Accepted Manuscript
Journal Name:
Vaccine
Additional Journal Information:
Journal Volume: 35; Journal Issue: 11; Journal ID: ISSN 0264-410X
Publisher:
Elsevier
Research Org:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org:
USDOE Office of Electricity Delivery and Energy Reliability (OE), Power Systems Engineering Research and Development (R&D) (OE-10)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 77 NANOSCIENCE AND NANOTECHNOLOGY; Nanolipoprotein; Nanoparticle; Intranasal; Vaccine; T cell activation; Nanodisc
OSTI Identifier:
1409999
Alternate Identifier(s):
OSTI ID: 1397843