title: Development of immune response that protects mice from viral pneumonitis after a single intranasal immunization with influenza A virus and nanoemulsion.
abstract: Nanoemulsion, a water-in-oil formulation stabilized by small amounts of surfactant, is non-toxic to mucous membranes and produces biocidal activity against enveloped viruses. We evaluated nanoemulsion as an adjuvant for mucosal influenza vaccines. Mice (C3H/HeNHsd strain) were vaccinated intranasally with 5 x 10(5) plaque forming units (pfu) of influenza A virus (Ann Arbor/6/60 strain) and a nanoemulsion mixture. The mice were challenged on day 21 after immunization with an intranasal lethal dose of 2 x 10(5) pfu of virus. Animals vaccinated with the influenza A/nanoemulsion mixture were completely protected against infection, while animals vaccinated with either formaldehyde-killed virus or nanoemulsion alone developed viral pneumonitis and died by day 6 after the challenge. Mice vaccinated with virus/nanoemulsion mixture had rapid cytokine responses followed by high levels of specific anti-influenza immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies. Specificity of the immune response was confirmed by assessment of the proliferation and cytokine production in splenocytes. This paper demonstrates that nanoemulsion can be employed as a non-toxic mucosal adjuvant for influenza virus vaccine.
authors.affiliation: Department of Internal Medicine, Division of Allergy, Center of Biologic Nanotechnology, University of Michigan, 9240 MSRB III,, Ann Arbor, MI 48109-0666, USA.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Myc
authors.forename: Jolanta F
authors.initials: JF
authors.lastname: Kukowska-Latallo
authors.forename: Anna U
authors.initials: AU
authors.lastname: Bielinska
authors.forename: Peter
authors.initials: P
authors.lastname: Cao
authors.forename: Piotr P
authors.initials: PP
authors.lastname: Myc
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Janczak
authors.forename: Tracy R
authors.initials: TR
authors.lastname: Sturm
authors.forename: Michael S
authors.initials: MS
authors.lastname: Grabinski
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Landers
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Young
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chang
authors.forename: Tarek
authors.initials: T
authors.lastname: Hamouda
authors.forename: Michal A
authors.initials: MA
authors.lastname: Olszewski
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D000918:Antibody Specificity; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000821:virology; D002455:Cell Division / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D004655:Emulsions; D005260:Female; D005434:Flow Cytometry; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology; D007114:Immunization; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology* / Q000633:toxicity; D051379:Mice; D008809:Mice, Inbred C3H; D011014:Pneumonia / Q000276:immunology / Q000517:prevention & control*; D012367:RNA, Viral / Q000032:analysis / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D010948:Viral Plaque Assay
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D004655:Emulsions; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D012367:RNA, Viral; D015164:Vaccines, Inactivated