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

Weilhammer, Dina; Dunkle, Alexis D.; Blanchette, Craig D.; Fischer, Nicholas O.; Corzett, Michele; Lehmann, Doerte; Boone, Tyler; Hoeprich, Paul; Driks, Adam; Rasley, Amy

doi:10.1016/j.vaccine.2017.02.004

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

Journal Article · Mon Feb 13 23:00:00 EST 2017 · Vaccine

DOI:https://doi.org/10.1016/j.vaccine.2017.02.004· OSTI ID:1409999

Weilhammer, Dina ^[1]; Dunkle, Alexis D. ^[1]; Blanchette, Craig D. ^[1]; Fischer, Nicholas O. ^[1]; Corzett, Michele ^[1]; Lehmann, Doerte ^[2]; Boone, Tyler ^[2]; Hoeprich, Paul ^[1]; Driks, Adam ^[2]; Rasley, Amy ^[1]

Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division
Loyola Univ. Medical Center, Maywood, IL (United States). Dept. of Microbiology & Immunology

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE Office of Electricity Delivery and Energy Reliability (OE), Power Systems Engineering Research and Development (R&D) (OE-10)

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 1409999

Alternate ID(s):: OSTI ID: 1397843

Report Number(s):: LLNL-JRNL--724260

Journal Information:: Vaccine, Journal Name: Vaccine Journal Issue: 11 Vol. 35; ISSN 0264-410X

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Cited By (2)

Lipid composition dictates serum stability of reconstituted high-density lipoproteins: implications for in vivo applications Gilmore, Sean F.; Carpenter, Timothy S.; Ingólfsson, Helgi I. Nanoscale, Vol. 10, Issue 16 https://doi.org/10.1039/c7nr09690a	journal	January 2018
Extent of MHC Clustering Regulates Selectivity and Effectiveness of T Cell Responses Anikeeva, Nadia; Fischer, Nicholas O.; Blanchette, Craig D. The Journal of Immunology, Vol. 202, Issue 2 https://doi.org/10.4049/jimmunol.1801196	journal	December 2018

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Related Subjects

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