title: Induction of systemic and mucosal immunity and maintenance of its memory against influenza A virus by nasal vaccination using a new mucosal adjuvant SF-10 derived from pulmonary surfactant in young cynomolgus monkeys.
abstract: Induction of systemic and mucosal immunity and maintenance of its memory was investigated in 12 young male cynomolgus monkeys after intranasal instillation of flu vaccine using a new mucosal adjuvant SF-10 derived from pulmonary surfactant constituents. Split-product of influenza virus A/California/7/2009(H1N1)pdm hemagglutinin vaccine (HAv) at 15 μg with or without SF-10 and the adjuvant alone were instilled intranasally three times every 2 weeks. SF-10-adjuvanted HAv (SF-10-HAv) elicited significantly higher HAv-specific IgG and hemagglutinin inhibition (HI) titers in serum and HAv-specific secretory IgA and its neutralizing activities in nasal washes compared with HAv antigen and SF-10 alone. Significant cross-neutralizing activities of nasal washes after the third vaccination to several other H1N1 and H3N2 strains were observed. HI titers in serum and neutralizing activities in nasal washes reached peak levels at 6 weeks after initial vaccination, then gradually decreased after 10 weeks and returned to the baseline levels at 36 weeks. A single intranasal revaccination of SF-10-HAv at 36 weeks rapidly and significantly increased both immunity in serum and nasal washes compared with naïve monkeys. Revaccination by one or two doses achieved almost maximal immunity at 2 or 4 weeks after instillation. Statistically significant adverse effects (e.g., body weight loss, elevated body temperature, nasal discharge, change in peripheral blood leukocyte and platelet counts) were not observed for 2 weeks after vaccination of SF-10-HAv, HAv or SF-10 and also during the experimental period. These results in young monkey model suggest the potential of clinical use SF-10 for intranasal flu vaccine.
authors.affiliation: Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Kuramoto-cho 3-18-15, Tokushima 770-8503, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Mizuno
authors.affiliation: Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Kuramoto-cho 3-18-15, Tokushima 770-8503, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kimoto
authors.affiliation: Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Kuramoto-cho 3-18-15, Tokushima 770-8503, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Kuramoto-cho 3-18-15, Tokushima 770-8503, Japan.
authors.forename: Etsuhisa
authors.initials: E
authors.lastname: Takahashi
authors.affiliation: Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Kuramoto-cho 3-18-15, Tokushima 770-8503, Japan.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Kuramoto-cho 3-18-15, Tokushima 770-8503, Japan. Electronic address: kido@tokushima-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kido
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D056738:Cross Protection; D006385:Hemagglutination Inhibition Tests; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D053118:Influenza A Virus, H1N1 Subtype; D053122:Influenza A Virus, H3N2 Subtype; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008252:Macaca fascicularis; D008297:Male; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D011663:Pulmonary Surfactants / Q000276:immunology*; D014611:Vaccination / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D011663:Pulmonary Surfactants
keywords: Cross-neutralization; Cynomolgus monkey; Mucosal adjuvant; Nasal influenza vaccination; Pulmonary surfactant; Revaccination