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. 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.affiliation: Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, United States.
authors.forename: Dina
authors.initials: D
authors.lastname: Weilhammer
authors.affiliation: Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, United States.
authors.forename: Alexis D
authors.initials: AD
authors.lastname: Dunkle
authors.affiliation: Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, United States.
authors.forename: Craig D
authors.initials: CD
authors.lastname: Blanchette
authors.affiliation: Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, United States.
authors.forename: Nicholas O
authors.initials: NO
authors.lastname: Fischer
authors.affiliation: Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, United States.
authors.forename: Michele
authors.initials: M
authors.lastname: Corzett
authors.affiliation: Department of Microbiology & Immunology, Loyola University Medical Center, United States.
authors.forename: Doerte
authors.initials: D
authors.lastname: Lehmann
authors.affiliation: Department of Microbiology & Immunology, Loyola University Medical Center, United States.
authors.forename: Tyler
authors.initials: T
authors.lastname: Boone
authors.affiliation: Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Hoeprich
authors.affiliation: Department of Microbiology & Immunology, Loyola University Medical Center, United States.
authors.forename: Adam
authors.initials: A
authors.lastname: Driks
authors.affiliation: Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, United States. Electronic address: Rasley2@llnl.gov.
authors.forename: Amy
authors.initials: A
authors.lastname: Rasley
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D001688:Biological Products / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053758:Nanoparticles / Q000008:administration & dosage*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D001688:Biological Products; D008050:Lipid A; D014612:Vaccines; D010047:Ovalbumin; C048436:monophosphoryl lipid A
keywords: Intranasal; Nanodisc; Nanolipoprotein; Nanoparticle; T cell activation; Vaccine