title: Enhanced pulmonary immunization with aerosolized inactivated influenza vaccine containing delta inulin adjuvant.
abstract: Vaccination is the primary intervention to contain influenza virus spread during seasonal and pandemic outbreaks. Pulmonary vaccination is gaining increasing attention for its ability to induce both local mucosal and systemic immune responses without the need for invasive injections. However, pulmonary administration of whole inactivated influenza virus (WIV) vaccine induces a Th2 dominant systemic immune response while a more balanced Th1/Th2 vaccine response may be preferred and only induces modest nasal immunity. This study evaluated immunity elicited by pulmonary versus intramuscular (i.m.) delivery of WIV, and tested whether the immune response could be improved by co-administration of delta (δ)-inulin, a novel carbohydrate-based particulate adjuvant. After pulmonary administration both unadjuvanted and δ-inulin adjuvanted WIV induced a potent systemic immune response, inducing higher serum anti-influenza IgG titers and nasal IgA titers than i.m. administration. Moreover, the addition of δ-inulin induced a more balanced Th1/Th2 response and induced higher nasal IgA titers versus pulmonary WIV alone. Pulmonary WIV alone or with δ-inulin induced hemagglutination inhibition (HI) titers>40, titers which are considered protective against influenza virus. In conclusion, in this study we have shown that δ-inulin adjuvanted WIV induces a better immune response after pulmonary administration than vaccine alone.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Senthil
authors.initials: S
authors.lastname: Murugappan
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.affiliation: Vaxine Pty Ltd., Flinders Medical Centre, Bedford Park, Adelaide 5042, Australia; Department of Diabetes and Endocrinology, Flinders Medical Centre/Flinders University, Adelaide 5042, Australia.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Petrovsky
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. Electronic address: w.l.j.hinrichs@rug.nl.
authors.forename: Wouter L J
authors.initials: WL
authors.lastname: Hinrichs
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D006385:Hemagglutination Inhibition Tests; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007444:Inulin / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000336:Aerosols; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D007444:Inulin
keywords: Adjuvant; Inulin; Pulmonary; Vaccination; Vaccine; Whole inactivated influenza virus