title: Rabbit nasal immunization against influenza by dry-powder form of chitosan nanospheres encapsulated with influenza whole virus and adjuvants.
abstract: Influenza virus is one of the main causes of respiratory diseases in human. Although different vaccines have been produced during past decades, there is still a huge demand for a safe influenza vaccine with the ability to induce mucosal immune responses and sufficient protection, especially in elderly patients. In this study, chitosan nanospheres were employed as the drug delivery system. Influenza virus, CpG oligodeoxynucleotide (CpG ODN) and Quillaja saponins (QS) were incorporated in this nanospheric system. Three doses of dry powder nanosphere vaccine were nasally administered to rabbits on days 0, 45 and 60, followed by a final booster injection on day 75. Both humoral and cellular immune responses were investigated. Hemagglutination inhibition (HI) antibody titer was elevated in all groups compared to the control group at the end of vaccination in rabbits receiving nanospheres loaded with virus and CpG, CH(WV+CpG) (P<0.001). Rabbit serum IgG raised significantly in all the vaccinated groups, with the highest responses in CH(WV+CpG) group. CH(WV+CpG) and CH(WV) induced significant sIgA titers (P<0.001). CpG adjuvant also showed a prominent role in the stimulation and secretion of of IL-2 and IFN-γ cytokines (3 and 3.5 fold increase, respectively). Finally, as CH(WV+CpG) depicted to be effective in induction of humoral and cellular immune responses after nasal administration, this nanoparticulate adjuvant could be identified as an efficient adjuvant/delivery system for mucosal immunization against influenza virus.
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Influenza Research Lab, Pasteur Institute of Iran, No. 358, 12th Farvardin Street, Jomhoori Avenue, Tehran 13169-43551, Iran.
authors.forename: Solmaz
authors.initials: S
authors.lastname: Dehghan
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Tafaghodi
authors.affiliation: Influenza Research Lab, Pasteur Institute of Iran, No. 358, 12th Farvardin Street, Jomhoori Avenue, Tehran 13169-43551, Iran.
authors.forename: Tina
authors.initials: T
authors.lastname: Bolourieh
authors.affiliation: Influenza Research Lab, Pasteur Institute of Iran, No. 358, 12th Farvardin Street, Jomhoori Avenue, Tehran 13169-43551, Iran.
authors.forename: Vahideh
authors.initials: V
authors.lastname: Mazaheri
authors.affiliation: Influenza Research Lab, Pasteur Institute of Iran, No. 358, 12th Farvardin Street, Jomhoori Avenue, Tehran 13169-43551, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Torabi
authors.affiliation: Pharmaceutical Sciences Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: Influenza Research Lab, Pasteur Institute of Iran, No. 358, 12th Farvardin Street, Jomhoori Avenue, Tehran 13169-43551, Iran. Electronic address: mtkheiri@gmail.com.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Tavassoti Kheiri
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage* / Q000627:therapeutic use; D004339:Drug Compounding; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D018928:Immunity, Mucosal / Q000187:drug effects; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000627:therapeutic use; D054118:Nanospheres / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000627:therapeutic use; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D011208:Powders; D062605:Quillaja Saponins / Q000008:administration & dosage / Q000627:therapeutic use; D011817:Rabbits; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; C408982:CPG-oligonucleotide; D004337:Drug Carriers; D007252:Influenza Vaccines; D009838:Oligodeoxyribonucleotides; D011208:Powders; D062605:Quillaja Saponins; D015164:Vaccines, Inactivated; D048271:Chitosan
keywords: Chitosan; Dry powder; Inactivated influenza virus; Nanospheres; Nasal vaccine delivery