title: Intranasal delivery of influenza subunit vaccine formulated with GEM particles as an adjuvant.
abstract: Nasal administration of influenza vaccine has the potential to facilitate influenza control and prevention. However, when administered intranasally (i.n.), commercially available inactivated vaccines only generate systemic and mucosal immune responses if strong adjuvants are used, which are often associated with safety problems. We describe the successful use of a safe adjuvant Gram-positive enhancer matrix (GEM) particles derived from the food-grade bacterium Lactococcus lactis for i.n. vaccination with subunit influenza vaccine in mice. It is shown that simple admixing of the vaccine with the GEM particles results in a strongly enhanced immune response. Already after one booster, the i.n. delivered GEM subunit vaccine resulted in hemagglutination inhibition titers in serum at a level equal to the conventional intramuscular (i.m.) route. Moreover, i.n. immunization with GEM subunit vaccine elicited superior mucosal and Th1 skewed immune responses compared to those induced by i.m. and i.n. administered subunit vaccine alone. In conclusion, GEM particles act as a potent adjuvant for i.n. influenza immunization.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, 9713 AV, Groningen, The Netherlands. v.saluja@rug.nl
authors.forename: Vinay
authors.initials: V
authors.lastname: Saluja
authors.forename: Jean P
authors.initials: JP
authors.lastname: Amorij
authors.forename: Maarten L
authors.initials: ML
authors.lastname: van Roosmalen
authors.forename: Kees
authors.initials: K
authors.lastname: Leenhouts
authors.forename: Anke
authors.initials: A
authors.lastname: Huckriede
authors.forename: Wouter L J
authors.initials: WL
authors.lastname: Hinrichs
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D002626:Chemistry, Pharmaceutical; D004797:Enzyme-Linked Immunosorbent Assay; D006385:Hemagglutination Inhibition Tests; D007114:Immunization; D007070:Immunoglobulin A / Q000032:analysis / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000737:chemistry; D007273:Injections, Intramuscular; D013294:Lactococcus lactis / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000276:immunology; D010641:Phenotype
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines