title: Synthetic mast-cell granules as adjuvants to promote and polarize immunity in lymph nodes.
abstract: Granules of mast cells (MCs) enhance adaptive immunity when, on activation, they are released as stable particles. Here we show that submicrometre particles modelled after MC granules augment immunity when used as adjuvants in vaccines. The synthetic particles, which consist of a carbohydrate backbone with encapsulated inflammatory mediators such as tumour necrosis factor, replicate attributes of MCs in vivo including the targeting of draining lymph nodes and the timed release of the encapsulated mediators. When used as an adjuvant during vaccination of mice with haemagglutinin from the influenza virus, the particles enhanced adaptive immune responses and increased survival of mice on lethal challenge. Furthermore, differential loading of the particles with the cytokine IL-12 directed the character of the response towards Th1 lymphocytes. The synthetic MC adjuvants replicate and enhance the functions of MCs during vaccination, and can be extended to polarize the resulting immunity.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA. ashley.st.john@duke.edu
authors.forename: Ashley L
authors.initials: AL
authors.lastname: St John
authors.forename: Cheryl Y
authors.initials: CY
authors.lastname: Chan
authors.forename: Herman F
authors.initials: HF
authors.lastname: Staats
authors.forename: Kam W
authors.initials: KW
authors.lastname: Leong
authors.forename: Soman N
authors.initials: SN
authors.lastname: Abraham
mesh_terms: D056704:Adaptive Immunity; D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D005260:Female; D018664:Interleukin-12 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D008407:Mast Cells / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000276:Adjuvants, Immunologic; D018664:Interleukin-12