title: Methylglycol chitosan and a synthetic TLR4 agonist enhance immune responses to influenza vaccine administered sublingually.
abstract: Influenza is a vaccine-preventable contagious respiratory illness caused by influenza (flu) viruses which can lead to hospitalization and sometimes even death. Current flu vaccines delivered intramuscularly (IM) or intradermally (ID) are less effective at eliciting protective mucosal immune responses and vaccines delivered intranasally (IN) possess potential safety concerns. Sublingual (SL) vaccination is a promising alternative route for vaccine delivery which has been indicated as safe and effective at inducing protective immune responses in both systemic and mucosal compartments. We evaluated the efficacy of methylglycol chitosan (MGC) and a synthetic toll-like receptor 4 agonist (CRX-601), alone or in combination, for improving systemic and mucosal immune responses to a monovalent detergent-split flu virus vaccine delivered SL. SL vaccination of mice with split-flu vaccine formulated with either MGC or CRX-601 resulted in specific serum IgG and mucosal IgA titers that were significantly greater than titers from non-adjuvanted vaccination and equivalent to or greater than titers in mice vaccinated IM. Our results demonstrate that SL vaccination utilizing MGC or CRX-601 as adjuvants is a viable alternative route of vaccination for flu which can elicit systemic immune responses equivalent to or greater than IM vaccination with the added benefit of stimulating a robust specific mucosal immune response.
authors.affiliation: GlaxoSmithKline Vaccines, 553 Old Corvallis Road, Hamilton, MT 59840, USA.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Spinner
authors.affiliation: 1910 Country Drive Apartment 202, Grayslake, IL 60030, USA.
authors.forename: Hardeep S
authors.initials: HS
authors.lastname: Oberoi
authors.affiliation: 3067 Bugli Lane, Stevensville, MT 59870, USA.
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Yorgensen
authors.affiliation: GlaxoSmithKline Vaccines, 525 Cartier Ouest, Laval, QC, Canada H7V 3S8.
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Poirier
authors.affiliation: GlaxoSmithKline Vaccines, 553 Old Corvallis Road, Hamilton, MT 59840, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Burkhart
authors.affiliation: Neomed Institute, 7171 Frederick Banting, Montreal, QC, Canada H4S 1Z9.
authors.forename: Martin
authors.initials: M
authors.lastname: Plante
authors.affiliation: GlaxoSmithKline Vaccines, 553 Old Corvallis Road, Hamilton, MT 59840, USA. Electronic address: jay.t.evans@gsk.com.
authors.forename: Jay T
authors.initials: JT
authors.lastname: Evans
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000286:Administration, Sublingual; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D048271:Chitosan / Q000008:administration & dosage*; D005260:Female; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008807:Mice, Inbred BALB C; D051197:Toll-Like Receptor 4 / Q000819:agonists*; D016896:Treatment Outcome; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D015164:Vaccines, Inactivated; C041606:methylglycol chitosan; D048271:Chitosan
keywords: CRX-601; Chitosan; Influenza; Mucosal vaccination; Sublingual; TLR-4