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

Abstract

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:
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)
OSTI Identifier:
1409999
Alternate Identifier(s):
OSTI ID: 1397843
Report Number(s):
LLNL-JRNL-724260
Journal ID: ISSN 0264-410X
Grant/Contract Number:  
AC52-07NA27344
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Vaccine
Additional Journal Information:
Journal Volume: 35; Journal Issue: 11; Journal ID: ISSN 0264-410X
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 77 NANOSCIENCE AND NANOTECHNOLOGY; Nanolipoprotein; Nanoparticle; Intranasal; Vaccine; T cell activation; Nanodisc

Citation Formats

Weilhammer, Dina, Dunkle, Alexis D., Blanchette, Craig D., Fischer, Nicholas O., Corzett, Michele, Lehmann, Doerte, Boone, Tyler, Hoeprich, Paul, Driks, Adam, and Rasley, Amy. Enhancement of antigen-specific CD4+ and CD8+ T cell responses using a self-assembled biologic nanolipoprotein particle vaccine. United States: N. p., 2017. Web. doi:10.1016/j.vaccine.2017.02.004.
Weilhammer, Dina, Dunkle, Alexis D., Blanchette, Craig D., Fischer, Nicholas O., Corzett, Michele, Lehmann, Doerte, Boone, Tyler, Hoeprich, Paul, Driks, Adam, & Rasley, Amy. Enhancement of antigen-specific CD4+ and CD8+ T cell responses using a self-assembled biologic nanolipoprotein particle vaccine. United States. doi:10.1016/j.vaccine.2017.02.004.
Weilhammer, Dina, Dunkle, Alexis D., Blanchette, Craig D., Fischer, Nicholas O., Corzett, Michele, Lehmann, Doerte, Boone, Tyler, Hoeprich, Paul, Driks, Adam, and Rasley, Amy. Tue . "Enhancement of antigen-specific CD4+ and CD8+ T cell responses using a self-assembled biologic nanolipoprotein particle vaccine". United States. doi:10.1016/j.vaccine.2017.02.004. https://www.osti.gov/servlets/purl/1409999.
@article{osti_1409999,
title = {Enhancement of antigen-specific CD4+ and CD8+ T cell responses using a self-assembled biologic nanolipoprotein particle vaccine},
author = {Weilhammer, Dina and Dunkle, Alexis D. and Blanchette, Craig D. and Fischer, Nicholas O. and Corzett, Michele and Lehmann, Doerte and Boone, Tyler and Hoeprich, Paul and Driks, Adam and Rasley, Amy},
abstractNote = {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.},
doi = {10.1016/j.vaccine.2017.02.004},
journal = {Vaccine},
number = 11,
volume = 35,
place = {United States},
year = {Tue Feb 14 00:00:00 EST 2017},
month = {Tue Feb 14 00:00:00 EST 2017}
}

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