title: Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses.
abstract: Vaccines based on recombinant proteins avoid the toxicity and antivector immunity associated with live vaccine (for example, viral) vectors, but their immunogenicity is poor, particularly for CD8(+) T-cell responses. Synthetic particles carrying antigens and adjuvant molecules have been developed to enhance subunit vaccines, but in general these materials have failed to elicit CD8(+) T-cell responses comparable to those for live vectors in preclinical animal models. Here, we describe interbilayer-crosslinked multilamellar vesicles formed by crosslinking headgroups of adjacent lipid bilayers within multilamellar vesicles. Interbilayer-crosslinked vesicles stably entrapped protein antigens in the vesicle core and lipid-based immunostimulatory molecules in the vesicle walls under extracellular conditions, but exhibited rapid release in the presence of endolysosomal lipases. We found that these antigen/adjuvant-carrying vesicles form an extremely potent whole-protein vaccine, eliciting endogenous T-cell and antibody responses comparable to those for the strongest vaccine vectors. These materials should enable a range of subunit vaccines and provide new possibilities for therapeutic protein delivery.
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Moon
authors.forename: Heikyung
authors.initials: H
authors.lastname: Suh
authors.forename: Anna
authors.initials: A
authors.lastname: Bershteyn
authors.forename: Matthias T
authors.initials: MT
authors.lastname: Stephan
authors.forename: Haipeng
authors.initials: H
authors.lastname: Liu
authors.forename: Bonnie
authors.initials: B
authors.lastname: Huang
authors.forename: Mashaal
authors.initials: M
authors.lastname: Sohail
authors.forename: Samantha
authors.initials: S
authors.lastname: Luo
authors.forename: Soong Ho
authors.initials: SH
authors.lastname: Um
authors.forename: Htet
authors.initials: H
authors.lastname: Khant
authors.forename: Jessica T
authors.initials: JT
authors.lastname: Goodwin
authors.forename: Jenelyn
authors.initials: J
authors.lastname: Ramos
authors.forename: Wah
authors.initials: W
authors.lastname: Chiu
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Irvine
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry; D000818:Animals; D004337:Drug Carriers; D015195:Drug Design; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007156:Immunologic Memory; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry* / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*; D014765:Viral Vaccines / Q000737:chemistry / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D008051:Lipid Bilayers; D008081:Liposomes; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D010047:Ovalbumin