title: Co-immunization with an optimized plasmid-encoded immune stimulatory interleukin, high-mobility group box 1 protein, results in enhanced interferon-gamma secretion by antigen-specific CD8 T cells.
abstract: DNA vaccination is a novel immunization strategy that has great potential for the development of vaccines and immune therapeutics. This strategy has been highly effective in mice, but is less immunogenic in non-human primates and in humans. Enhancing DNA vaccine potency remains a challenge. It is likely that antigen-presenting cells (APCs), and especially dendritic cells (DCs), play a significant role in the presentation of the vaccine antigen to the immune system. A new study reports the synergistic recruitment, expansion and activation of DCs in vivo by high-mobility group box 1 (HMGB1) protein. Such combinational strategies for delivering vaccine in a single, simple platform will hypothetically bolster the cellular immunity in vivo. Here, we combined plasmid encoding human immunodeficiency virus-1 (HIV-1) Gag and Env with an HMGB1 plasmid as a DNA adjuvant in BALB/c mice (by intramuscular immunization via electroporation), and humoral and cellular responses were measured. Co-administration of this potent immunostimulatory adjuvant strongly enhanced the cellular interferon-gamma (IFN-gamma) and humoral immune response compared with that obtained in mice immunized with vaccine only. Our results show that co-immunization with HMGB1 can have a strong adjuvant activity, driving strong cellular and humoral immunity that may be an effective immunological adjuvant in DNA vaccination against HIV-1.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. gmuthumani@gmail.com
authors.forename: Gowtham
authors.initials: G
authors.lastname: Muthumani
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Laddy
authors.forename: Senthil G
authors.initials: SG
authors.lastname: Sundaram
authors.forename: Paolo
authors.initials: P
authors.lastname: Fagone
authors.forename: Devon J
authors.initials: DJ
authors.lastname: Shedlock
authors.forename: Senthil
authors.initials: S
authors.lastname: Kannan
authors.forename: Ling
authors.initials: L
authors.lastname: Wu
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Chung
authors.forename: Karthikbabu Mallil
authors.initials: KM
authors.lastname: Lankaraman
authors.forename: John
authors.initials: J
authors.lastname: Burns
authors.forename: Karuppiah
authors.initials: K
authors.lastname: Muthumani
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D024243:HMGB1 Protein / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000378:metabolism; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000378:metabolism
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000906:Antibodies; D024243:HMGB1 Protein; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma