title: PEG modified liposomes containing CRX-601 adjuvant in combination with methylglycol chitosan enhance the murine sublingual immune response to influenza vaccination.
abstract: The mucosa is the primary point of entry for pathogens making it an important vaccination site to produce a protective mucosal immune response. While the sublingual (SL) mucosa presents several barriers to vaccine penetration, its unique anatomy and physiology makes it one of the best options for mucosal vaccination. Efficient and directed delivery of adjuvants and antigens to appropriate immune mediators in the SL tissue will aid in development of effective SL vaccines against infectious diseases. Herein we demonstrate a robust immune response against influenza antigens co-delivered sublingually with engineered liposomes carrying the synthetic Toll-like receptor-4 agonist, CRX-601. Liposome modification with PEG copolymers (Pluronics), phospholipid-PEG conjugates and chitosan were evaluated for their ability to generate an immune response in a SL murine influenza vaccine model. Phospholipid-PEG conjugates were more effective than Pluronic copolymers in generating stable, surface neutral liposomes. SL vaccination with surface modified liposomes carrying CRX-601 adjuvant generated significant improvements in flu-specific responses compared with unmodified liposomes. Furthermore, the coating of modified liposomes with methylglycol chitosan produced the most effective flu-specific immune response. These results demonstrate efficient SL vaccine delivery utilizing a combination of a muco-adhesive and surface neutral liposomes to achieve a robust mucosal and systemic immune response.
authors.affiliation: GSK Vaccines, 553 Old Corvallis Road, Hamilton, MT 59840, USA.
authors.forename: Hardeep S
authors.initials: HS
authors.lastname: Oberoi
authors.affiliation: GSK Vaccines, 553 Old Corvallis Road, Hamilton, MT 59840, USA.
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Yorgensen
authors.affiliation: GSK Vaccines, 525 Boulevard Cartier, Laval, QC H7V 3S8, Canada.
authors.forename: Audrey
authors.initials: A
authors.lastname: Morasse
authors.affiliation: GSK Vaccines, 553 Old Corvallis Road, Hamilton, MT 59840, USA.
authors.forename: Jay T
authors.initials: JT
authors.lastname: Evans
authors.affiliation: GSK Vaccines, 553 Old Corvallis Road, Hamilton, MT 59840, USA. Electronic address: david.j.burkhart@gsk.com.
authors.forename: David J
authors.initials: DJ
authors.lastname: Burkhart
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000286:Administration, Sublingual; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D005958:Glucosephosphates / Q000008:administration & dosage*; D006017:Glycolipids / Q000008:administration & dosage*; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage*; D008081:Liposomes; D008807:Mice, Inbred BALB C; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011817:Rabbits; D051197:Toll-Like Receptor 4 / Q000276:immunology; D014611:Vaccination / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D005958:Glucosephosphates; D006017:Glycolipids; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D008081:Liposomes; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D020442:Poloxamer; D011092:Polyethylene Glycols; C041606:methylglycol chitosan; D048271:Chitosan
keywords: Chitosan; Influenza; Liposomes; Mucosal; Sublingual; TLR4; Vaccine