Development of immune response that protects mice from viral pneumonitis after a single intranasal immunization with influenza A virus and nanoemulsion.
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.
Myc
Andrzej
A
Department of Internal Medicine, Division of Allergy, Center of Biologic Nanotechnology, University of Michigan, 9240 MSRB III,, Ann Arbor, MI 48109-0666, USA.
Kukowska-Latallo
Jolanta F
JF
Bielinska
Anna U
AU
Cao
Peter
P
Myc
Piotr P
PP
Janczak
Katarzyna
K
Sturm
Tracy R
TR
Grabinski
Michael S
MS
Landers
Jeffrey J
JJ
Young
Katherine S
KS
Chang
Jennifer
J
Hamouda
Tarek
T
Olszewski
Michal A
MA
Baker
James R
JR
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
D000276:Adjuvants, Immunologic; D016207:Cytokines; D004655:Emulsions; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D012367:RNA, Viral; D015164:Vaccines, Inactivated