title: Molecular adjuvant IL-33 enhances the potency of a DNA vaccine in a lethal challenge model.
abstract: Identifying new molecular adjuvants that elicit effective vaccine-induced CD8(+) T cell immunity may be critical for the elimination of many challenging diseases including Tuberculosis, HIV and cancer. Here, we report that co-administration of molecular adjuvant IL-33 during vaccination enhanced the magnitude and function of antigen (Ag)-specific CD8(+) T cells against a model Ag, LCMV NP target protein. These enhanced responses were characterized by higher frequencies of Ag-specific, polyfunctional CD8(+) T cells exhibiting cytotoxic characteristics. Importantly, these cells were capable of robust expansion upon Ag-specific restimulation in vivo and conferred remarkable protection against a high dose lethal LCMV challenge. In addition, we demonstrate the ability of IL-33 to amplifying the frequency of Ag-specific KLRG1(+) effector CD8(+) T cells. These data show that IL-33 is a promising immunoadjuvant at improving T cell immunity in a vaccine setting and suggest further development and understanding of this molecular adjuvant for strategies against many obstinate infectious diseases and cancer.
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Villarreal
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Tumor Microenvironment and Metastasis Program, Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Svoronos
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Megan C
authors.initials: MC
authors.lastname: Wise
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Devon J
authors.initials: DJ
authors.lastname: Shedlock
authors.affiliation: Inovio Pharmaceuticals, Inc., 660 West Germantown Pike, Suite 110, Plymouth Meeting, PA 19462, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Morrow
authors.affiliation: Tumor Microenvironment and Metastasis Program, Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Conejo-Garcia
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: dbweiner@mail.med.upenn.edu.
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000276:Adjuvants, Immunologic; D000818:Animals; D001117:Arenaviridae Infections / Q000517:prevention & control; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D007111:Immunity, Cellular; D007156:Immunologic Memory; D000067596:Interleukin-33 / Q000235:genetics / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D008810:Mice, Inbred C57BL; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000067596:Interleukin-33; D019444:Vaccines, DNA
keywords: Adjuvants; CD8 T cells; DNA vaccines; HIV; IL-33; LCMV