Enhancement of antigen-specific CD4+ and CD8+ T cell responses using a self-assembled biologic nanolipoprotein particle vaccine |
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| Institution: | 1. Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, United States;2. Department of Microbiology & Immunology, Loyola University Medical Center, United States;1. Sibley School of Mechanical and Aerospace Engineer, Cornell University, Ithaca, NY, USA;2. Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA;3. Applied Engineering Physics, Cornell University, Ithaca, NY, USA;4. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA;1. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA;2. Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA;3. Department of Biology, Boston College, Chestnut Hill, MA 02467, USA;4. Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA;5. Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA;1. Laboratory for Visual Neuroplasticity, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA;2. Department of Psychology, University of Milano-Bicocca, Milano, Italy;3. Brain Connectivity Center, National Neurological Institute C. Mondino, Pavia, Italy;4. Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy;1. Department of Medicinal Chemistry, School of Pharmacy, University of Washington, H-172 Health Sciences Building, Box 357610, Seattle, WA 98195, United States;2. Department of Pharmaceutics, School of Pharmacy, University of Washington, H272 Health Sciences Building, Box 357610, Seattle, WA 98195, United States |
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| 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. 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. |
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| Keywords: | Nanolipoprotein Nanoparticle Intranasal Vaccine T cell activation Nanodisc |
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