title: Evaluation of the effectiveness and safety of chitosan derivatives as adjuvants for intranasal vaccines.
abstract: Intranasal immunization is currently used to deliver live virus vaccines such as influenza. However, to develop an intranasal vaccine to deliver inactivated virus, a safe and effective adjuvant is necessary to enhance the mucosal immune response. Here, we demonstrate the effectiveness of a chitosan microparticle (1-20 μm, 50 kDa, degree of deacetylation=85%) and a cationized chitosan (1000 kDa, degree of deacetylation=85%) derived from natural crab shells as adjuvants for an intranasal vaccine candidate. We examined the effectiveness of chitosan derivatives as an adjuvant by co-administering them with ovalbumin (OVA) intranasally in BALB/c mice, polymeric Ig receptor knockout (pIgR-KO) mice, and cynomolgus monkeys (Macaca fascicularis). pIgR-KO mice were used to evaluate S-IgA production on the mucosal surface without nasal swab collection. Administration of OVA with chitosan microparticles or cationized chitosan induced a high OVA-specific IgA response in the serum of pIgR-KO mice and a high IgG response in the serum of BALB/c mice and cynomolgus monkeys. We also found that administration of chitosan derivatives did not have a detrimental effect on cynomolgus monkeys as determined by complete blood count, blood chemistries, and gross pathology results. These results suggest that chitosan derivatives are safe and effective mucosal adjuvants for intranasal vaccination.
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Fukushima
authors.forename: Takanori
authors.initials: T
authors.lastname: Sannan
authors.forename: Noriko
authors.initials: N
authors.lastname: Saito
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Takiguchi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Ishikawa
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects*; D000281:Administration, Intranasal; D000818:Animals; D048271:Chitosan / Q000008:administration & dosage* / Q000009:adverse effects* / Q000737:chemistry; D005260:Female; D007071:Immunoglobulin A, Secretory / Q000032:analysis / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008252:Macaca fascicularis; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008970:Molecular Weight; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D019056:Receptors, Polymeric Immunoglobulin / Q000172:deficiency
chemical_list: D000276:Adjuvants, Immunologic; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D019056:Receptors, Polymeric Immunoglobulin; D010047:Ovalbumin; D048271:Chitosan