title: Sublingual immunization with a subunit influenza vaccine elicits comparable systemic immune response as intramuscular immunization, but also induces local IgA and TH17 responses.
abstract: Influenza is a vaccine-preventable disease that remains a major health problem world-wide. Needle and syringe are still the primary delivery devices, and injection of liquid vaccine into the muscle is still the primary route of immunization. Vaccines could be more convenient and effective if they were delivered by the mucosal route. Elicitation of systemic and mucosal innate and adaptive immune responses, such as pathogen neutralizing antibodies (including mucosal IgA at the site of pathogen entry) and CD4(+) T-helper cells (especially the Th17 subset), have a critical role in vaccine-mediated protection. In the current study, a sublingual subunit influenza vaccine formulated with or without mucosal adjuvant was evaluated for systemic and mucosal immunogenicity and compared to intranasal and intramuscular vaccination. Sublingual administration of adjuvanted influenza vaccine elicited comparable antibody titers to those elicited by intramuscular immunization with conventional influenza vaccine. Furthermore, influenza-specific Th17 cells or neutralizing mucosal IgA were detected exclusively after mucosal immunization.
authors.affiliation: Vaccines Research, Novartis Vaccines, Siena, Italy. Electronic address: simona.gallorini@novartis.com.
authors.forename: Simona
authors.initials: S
authors.lastname: Gallorini
authors.affiliation: Vaccines Research, Novartis Vaccines, Siena, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Taccone
authors.affiliation: Vaccines Research, Novartis Vaccines, Siena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bonci
authors.affiliation: Vaccines Research, Novartis Vaccines, Siena, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Nardelli
authors.affiliation: Vaccines Research, Novartis Vaccines, Siena, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Casini
authors.affiliation: Vaccines Research, Novartis Vaccines, Cambridge, Massachusetts, United States.
authors.forename: Amanda
authors.initials: A
authors.lastname: Bonificio
authors.affiliation: Vaccines Research, Novartis Vaccines, Cambridge, Massachusetts, United States.
authors.forename: Sushma
authors.initials: S
authors.lastname: Kommareddy
authors.affiliation: Vaccines Research, Novartis Vaccines, Siena, Italy.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bertholet
authors.affiliation: Vaccines Research, Novartis Vaccines, Cambridge, Massachusetts, United States.
authors.forename: Derek T
authors.initials: DT
authors.lastname: O'Hagan
authors.affiliation: Vaccines Research, Novartis Vaccines, Siena, Italy.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Baudner
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000286:Administration, Sublingual; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D058504:Th17 Cells / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007252:Influenza Vaccines; D022223:Vaccines, Subunit
keywords: Influenza; Mucosal IgA; Sublingual; Subunit-vaccine; Th17 response